Skip to main content

T Cell Responses During Human Immunodeficiency Virus (HIV)-1 Infection

  • Chapter
  • First Online:
Control of Innate and Adaptive Immune Responses during Infectious Diseases

Abstract

The defining features of the acquired immunodeficiency are the “­persistent and profound selective decrease in the function as well as number of T lymphocytes of the helper/inducer subset and a possible activation of the suppressor/cytotoxic subset”, as described in 1982 (Mildvan, D., U. Mathur, et al. (1982). “Opportunistic infections and immune deficiency in homosexual men.” Ann Intern Med 96(6 Pt 1): 700–4). Nowadays, although depletion of CD4+ T-cells remains a hallmark of Human Immunodeficiency Virus (HIV) infection, the multifactorial nature of the disease provoked by infection by HIV-1 or Simian Immunodeficiency Virus (SIV) in “non-natural” hosts is generally acknowledged, in that no unique immune alteration has been identified that can fully explain the plethora of dysregulation associated with the development of pathogenic HIV and SIV infection.

This review will focus on what we know (or do not know) about T cell responses during HIV infection. This choice reflects the main expertise of the authors, and the major theme of this book. However, other aspects of adaptive and innate immunity should not be overlooked. Notably, HIV-specific antibodies, including neutralizing antibodies, are an important defense of the adaptive immune system, although HIV appears to quickly evade the effect of these antibodies. Recent studies have also highlighted the role of innate immunity in protection against HIV/SIV. In addition, several cellular antiretroviral restriction factors, either constitutively expressed or induced by interferons, have been identified, which provide considerable ­resistance to retroviral infection. For more on these topics, we refer readers to recent reviews summarizing these crucial aspects of the virus/host interaction (Kuritzkes, D. R. and B. D. Walker (2007). HIV-1 Pathogenesis, Clinical Manifestations and Treatment. Fields Virology. D. Knipe and P. M. Howley. Philadelphia, PA, Lippincott Williams & Wilkins. 2: 21872214; Levy, J. A. (2007). HIV and the Pathogenesis of AIDS. Washington, D.C., ASM Press; Zwick, M. B. and D. R. Burton (2007). “HIV-1 neutralization: mechanisms and relevance to vaccine design.” Curr HIV Res 5(6): 608–24; Alter, G. and M. Altfeld (2009). “NK cells in HIV-1 infection: evidence for their role in the control of HIV-1 ­infection.” J Intern Med 265(1): 29–42; Neil, S. and P. Bieniasz (2009). “Human immunodeficiency virus, restriction factors, and interferon.” J Interferon Cytokine Res 29(9): 569–80; Stamatatos, L., L. Morris, et al. (2009). “Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine?” Nat Med 15(8): 866–70; Strebel, K., J. Luban, et al. (2009). “Human cellular ­restriction factors that target HIV-1 replication.” BMC Med 7: 48; Altfeld, M., L. Fadda, et al. (2011). “DCs and NK cells: critical effectors in the immune response to HIV-1.” Nat Rev Immunol 11(3): 176–86).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aandahl, E. M., J. Michaelsson, et al. (2004). “Human CD4+ CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens.” J Virol 78(5): 2454–9.

    Article  PubMed  CAS  Google Scholar 

  • Abrams, D., Y. Levy, et al. (2009). “Interleukin-2 therapy in patients with HIV infection.” N Engl J Med 361(16): 1548–59.

    Article  PubMed  CAS  Google Scholar 

  • Allers, K., C. Loddenkemper, et al. (2010). “Gut mucosal FOXP3+ regulatory CD4+ T cells and Nonregulatory CD4+ T cells are differentially affected by simian immunodeficiency virus infection in rhesus macaques.” J Virol 84(7): 3259–69.

    Article  PubMed  CAS  Google Scholar 

  • Almeida, J. R., D. A. Price, et al. (2007). “Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover.” J Exp Med 204(10): 2473–85.

    Article  PubMed  CAS  Google Scholar 

  • Almeida, J. R., D. Sauce, et al. (2009). “Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity.” Blood 113(25): 6351–60.

    Article  PubMed  CAS  Google Scholar 

  • Alpert, M. D., A. R. Rahmberg, et al. (2010). “Envelope-modified single-cycle simian immunodeficiency virus selectively enhances antibody responses and partially protects against repeated, low-dose vaginal challenge.” J Virol 84(20): 10748–64.

    Article  PubMed  Google Scholar 

  • Alter, G. and M. Altfeld (2009). “NK cells in HIV-1 infection: evidence for their role in the control of HIV-1 infection.” J Intern Med 265(1): 29–42.

    Article  PubMed  CAS  Google Scholar 

  • Altfeld, M., L. Fadda, et al. (2011). “DCs and NK cells: critical effectors in the immune response to HIV-1.” Nat Rev Immunol 11(3): 176–86.

    Article  PubMed  CAS  Google Scholar 

  • Altfeld, M., E. T. Kalife, et al. (2006). “HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8(+) T Cell Response against HIV-1.” PLoS Med 3(10): e403.

    Article  PubMed  CAS  Google Scholar 

  • Andersson, J., A. Boasso, et al. (2005). “Cutting Edge: The Prevalence of Regulatory T Cells in Lymphoid Tissue Is Correlated with Viral Load in HIV-Infected Patients.” J Immunol 174(6): 3143–7.

    PubMed  CAS  Google Scholar 

  • Appay, V., D. C. Douek, et al. (2008). “CD8+ T cell efficacy in vaccination and disease.” Nat Med 14(6): 623–8.

    Article  PubMed  CAS  Google Scholar 

  • Appay, V. and S. L. Rowland-Jones (2002). “Premature ageing of the immune system: the cause of AIDS?” Trends Immunol 23(12): 580–5.

    Article  PubMed  CAS  Google Scholar 

  • Arhel, N. (2010). “Revisiting HIV-1 uncoating.” Retrovirology 7: 96.

    Article  PubMed  CAS  Google Scholar 

  • Arthos, J., C. Cicala, et al. (2008). “HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells.” Nat Immunol 9(3): 301–9.

    Article  PubMed  CAS  Google Scholar 

  • Arya, S. K., C. Guo, et al. (1985). “Trans-activator gene of human T-lymphotropic virus type III (HTLV-III).” Science 229(4708): 69–73.

    Article  PubMed  CAS  Google Scholar 

  • Badley, A. D., D. H. Dockrell, et al. (1998). “In vivo analysis of Fas/FasL interactions in HIV-infected patients.” J Clin Invest 102: 79–87.

    Article  PubMed  CAS  Google Scholar 

  • Banda, N. K., J. Bernier, et al. (1992). “Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis.” J Exp Med 176(4): 1099–106.

    Article  PubMed  CAS  Google Scholar 

  • Bangham, C. R. (2009). “CTL quality and the control of human retroviral infections.” Eur J Immunol 39(7): 1700–12.

    Article  PubMed  CAS  Google Scholar 

  • Barber, D. L., E. J. Wherry, et al. (2006). “Restoring function in exhausted CD8 T cells during chronic viral infection.” Nature 439(7077): 682–7.

    Article  PubMed  CAS  Google Scholar 

  • Barbour, J. D., U. Sriram, et al. (2007). “Synergy or independence? Deciphering the interaction of HLA Class I and NK cell KIR alleles in early HIV-1 disease progression.” PLoS Pathog 3(4): e43.

    Article  PubMed  CAS  Google Scholar 

  • Bashirova, A. A., R. Thomas, et al. (2011). “HLA/KIR Restraint of HIV: Surviving the Fittest.” Annu Rev Immunol.

    Google Scholar 

  • Betts, M. R., M. C. Nason, et al. (2006). “HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells.” Blood 107(12): 4781–9.

    Article  PubMed  CAS  Google Scholar 

  • Bhalerao, J. and A. M. Bowcock (1998). “The genetics of psoriasis: a complex disorder of the skin and immune system.” Hum Mol Genet 7(10): 1537–45.

    Article  PubMed  CAS  Google Scholar 

  • Blackburn, S. D., H. Shin, et al. (2009). “Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.” Nat Immunol 10(1): 29–37.

    Article  PubMed  CAS  Google Scholar 

  • Bleul, C. C., M. Farzan, et al. (1996). “The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry.” Nature 382(6594): 829–33.

    Article  PubMed  CAS  Google Scholar 

  • Boasso, A., A. W. Hardy, et al. (2008). “PDL-1 upregulation on monocytes and T cells by HIV via type I interferon: restricted expression of type I interferon receptor by CCR5-expressing leukocytes.” Clin Immunol 129(1): 132–44.

    Article  PubMed  CAS  Google Scholar 

  • Boasso, A., M. Vaccari, et al. (2007). “Regulatory T-cell markers, indoleamine 2,3-dioxygenase, and virus levels in spleen and gut during progressive simian immunodeficiency virus infection.” J Virol 81(21): 11593–603.

    Article  PubMed  CAS  Google Scholar 

  • Borrow, P., H. Lewicki, et al. (1997). “Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus [see comments].” Nat Med 3(2): 205–11.

    Article  PubMed  CAS  Google Scholar 

  • Bostik, P., P. Wu, et al. (2001). “Identification of protein kinases dysregulated in CD4(+) T cells in pathogenic versus apathogenic simian immunodeficiency virus infection.” J Virol 75(23): 11298–306.

    Article  PubMed  CAS  Google Scholar 

  • Brenchley, J. M. and D. C. Douek (2008). “The mucosal barrier and immune activation in HIV pathogenesis.” Curr Opin HIV AIDS 3(3): 356–61.

    Article  PubMed  Google Scholar 

  • Brenchley, J. M., M. Paiardini, et al. (2008). “Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections.” Blood 112(7): 2826–35.

    Article  PubMed  CAS  Google Scholar 

  • Brenchley, J. M., D. A. Price, et al. (2006). “Microbial translocation is a cause of systemic immune activation in chronic HIV infection.” Nat Med 12(12): 1365–71.

    Article  PubMed  CAS  Google Scholar 

  • Brenchley, J. M., T. W. Schacker, et al. (2004). “CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract.” J Exp Med 200(6): 749–59.

    Article  PubMed  CAS  Google Scholar 

  • Brenchley, J. M., G. Silvestri, et al. (2010). “Nonprogressive and progressive primate immunodeficiency lentivirus infections.” Immunity 32(6): 737–42.

    Article  PubMed  CAS  Google Scholar 

  • Brockman, M. A., A. Schneidewind, et al. (2007). “Escape and compensation from early HLA-B57-mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A.” J Virol 81(22): 12608–18.

    Article  PubMed  CAS  Google Scholar 

  • Carrington, M., M. P. Martin, et al. (2008). “KIR-HLA intercourse in HIV disease.” Trends Microbiol 16(12): 620–7.

    Article  PubMed  CAS  Google Scholar 

  • Cavrois, M., J. Neidleman, et al. (2008). “The achilles heel of the trojan horse model of HIV-1 trans-infection.” PLoS Pathog 4(6): e1000051.

    Article  PubMed  CAS  Google Scholar 

  • Cayota, A., F. Vuillier, et al. (1994). “Defective protein tyrosine phosphorylation and altered levels of p59fyn and p56lck in CD4 T cells from HIV-1 infected patients.” Int Immunol 6(4): 611–21.

    Article  PubMed  CAS  Google Scholar 

  • Cecchinato, V., E. Tryniszewska, et al. (2008). “Immune activation driven by CTLA-4 blockade augments viral replication at mucosal sites in simian immunodeficiency virus infection.” J immunol 180(8): 5439–47.

    PubMed  CAS  Google Scholar 

  • Chakrabarti, L., M. Guyader, et al. (1987). “Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses.” Nature 328(6130): 543–7.

    Article  PubMed  CAS  Google Scholar 

  • Chase, A. J., A. R. Sedaghat, et al. (2007). “Severe depletion of CD4+ CD25+ regulatory T cells from the intestinal lamina propria but not peripheral blood or lymph nodes during acute simian immunodeficiency virus infection.” J Virol 81(23): 12748–57.

    Article  PubMed  CAS  Google Scholar 

  • Chattopadhyay, P. K. and M. Roederer (2010). “Good cell, bad cell: flow cytometry reveals T-cell subsets important in HIV disease.” Cytometry A 77(7): 614–22.

    PubMed  Google Scholar 

  • Chessman, D., L. Kostenko, et al. (2008). “Human leukocyte antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity.” Immunity 28(6): 822–32.

    Article  PubMed  CAS  Google Scholar 

  • Chevalier, M. F., B. Julg, et al. (2011). “HIV-1-specific interleukin-21+ CD4+ T cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T cell function.” J Virol 85(2): 733–41.

    Article  PubMed  CAS  Google Scholar 

  • Chirmule, N., T. McCloskey, et al. (1995). “HIV gp120 inhibits T cell activation by interfering with expression of costimulatory molecules CD40 Ligand and CD80 (B7-1).” J Immunol 155: 917–924.

    PubMed  CAS  Google Scholar 

  • Chougnet, C., S. Jankelevich, et al. (2001). “Long-term protease inhibitor-containing therapy results in limited improvement in T cell function but not restoration of Interleukin-12 production in pediatric patients with AIDS.” J Infect Dis 184: 201–5.

    Article  PubMed  CAS  Google Scholar 

  • Clerici, M. and G. M. Shearer (1993). “A TH1--  >  TH2 switch is a critical step in the etiology of HIV infection [see comments].” Immunol Today 14(3): 107–11.

    Article  PubMed  CAS  Google Scholar 

  • Clumeck, N., A. Pozniak, et al. (2008). “European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of HIV-infected adults.” HIV Med 9(2): 65–71.

    Article  PubMed  CAS  Google Scholar 

  • Cohen, E. A., E. F. Terwilliger, et al. (1988). “Identification of a protein encoded by the vpu gene of HIV-1.” Nature 334(6182): 532–4.

    Article  PubMed  CAS  Google Scholar 

  • Collins, K. L., B. K. Chen, et al. (1998). “HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes.” Nature 391(6665): 397–401.

    Article  PubMed  CAS  Google Scholar 

  • Critchfield, J. W., D. Lemongello, et al. (2007). “Multifunctional HIVgag Specific CD8+ T-cell Responses in Rectal Mucosa and PBMC During Chronic HIV-1 Infection.” J Virol 81(11): 5460–5471.

    Article  PubMed  CAS  Google Scholar 

  • Critchfield, J. W., D. H. Young, et al. (2008). “Magnitude and complexity of rectal mucosa HIV-1-specific CD8+ T-cell responses during chronic infection reflect clinical status.” PLoS ONE 3(10): e3577.

    Article  PubMed  CAS  Google Scholar 

  • Crowe, S. M., J. B. Carlin, et al. (1991). “Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV-infected persons.” J Acquir Immune Defic Syndr 4(8): 770–6.

    PubMed  CAS  Google Scholar 

  • Cullen, B. R. (1991). “Human immunodeficiency virus as a prototypic complex retrovirus.” J Virol 65(3): 1053–6.

    PubMed  CAS  Google Scholar 

  • D’Souza, M., A. P. Fontenot, et al. (2007). “Programmed death 1 expression on HIV-specific CD4+ T cells is driven by viral replication and associated with T cell dysfunction.” J immunol 179(3): 1979–87.

    PubMed  Google Scholar 

  • Dabrowska, A., N. Kim, et al. (2008). “Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes.” J immunol 181(12): 8460–77.

    PubMed  CAS  Google Scholar 

  • Dalmasso, C., W. Carpentier, et al. (2008). “Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study.” PLoS One 3(12): e3907.

    Article  PubMed  CAS  Google Scholar 

  • Day, C. L., D. E. Kaufmann, et al. (2006). “PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression.” Nature 443(7109): 350–4.

    Article  PubMed  CAS  Google Scholar 

  • Decroly, E., M. Vandenbranden, et al. (1994). “The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM).” J Biol Chem 269(16): 12240–7.

    PubMed  CAS  Google Scholar 

  • Denton, P. W. and J. V. Garcia (2009). “Novel humanized murine models for HIV research.” Curr HIV/AIDS Rep 6(1): 13–9.

    Article  PubMed  Google Scholar 

  • di Marzo Veronese, F., T. D. Copeland, et al. (1986). “Characterization of highly immunogenic p66/p51 as the reverse transcriptase of HTLV-III/LAV.” Science 231(4743): 1289–91.

    Article  PubMed  Google Scholar 

  • Doherty, P. C. (1998). “The new numerology of immunity mediated by virus-specific CD8(+) T cells.” Curr Opin Microbiol 1(4): 419–22.

    Article  PubMed  CAS  Google Scholar 

  • Doitsh, G., M. Cavrois, et al. (2010). “Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue.” Cell 143(5): 789–801.

    Article  PubMed  CAS  Google Scholar 

  • Dolan, M., M. Clerici, et al. (1995). “A functional and phenotypic assessment of T-helper cells in HIV-1 infected patients offers independent pronostic information for survival.” J Infect Dis 172: 79–87.

    Article  PubMed  CAS  Google Scholar 

  • Douek, D. C., J. M. Brenchley, et al. (2002). “HIV preferentially infects HIV-specific CD4+ T cells.” Nature 417(6884): 95–8.

    Article  PubMed  CAS  Google Scholar 

  • Dragic, T., V. Litwin, et al. (1996). “HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5.” Nature 381(6584): 667–73.

    Article  PubMed  CAS  Google Scholar 

  • Eggena, M. P., B. Barugahare, et al. (2005). “Depletion of Regulatory T Cells in HIV Infection Is Associated with Immune Activation.” J Immunol 174(7): 4407–14.

    PubMed  CAS  Google Scholar 

  • Eggink, D., B. Berkhout, et al. (2010). “Inhibition of HIV-1 by fusion inhibitors.” Curr Pharm Des 16(33): 3716–28.

    Article  PubMed  CAS  Google Scholar 

  • Epple, H. J., C. Loddenkemper, et al. (2006). “Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART.” Blood 108(9): 3072–8.

    Article  PubMed  CAS  Google Scholar 

  • Estes, J., J. V. Baker, et al. (2008). “Collagen deposition limits immune reconstitution in the gut.” J Infect Dis 198(4): 456–64.

    Article  PubMed  Google Scholar 

  • Estes, J. D., L. D. Harris, et al. (2010). “Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections.” PLoS Pathog 6(8).

    Google Scholar 

  • Estes, J. D., Q. Li, et al. (2006). “Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection.” J Infect Dis 193(5): 703–12.

    Article  PubMed  CAS  Google Scholar 

  • Estes, J. D., S. Wietgrefe, et al. (2007). “Simian immunodeficiency virus-induced lymphatic tissue fibrosis is mediated by transforming growth factor beta 1-positive regulatory T cells and begins in early infection.” J Infect Dis 195(4): 551–61.

    Article  PubMed  CAS  Google Scholar 

  • Favre, D., S. Lederer, et al. (2009). “Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection.” PLoS Pathog 5(2): e1000295.

    Article  PubMed  CAS  Google Scholar 

  • Favre, D., J. Mold, et al. (2010). “Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease.” Sci Transl Med 2(32): 32ra36.

    Google Scholar 

  • Fellay, J., D. Ge, et al. (2009). “Common genetic variation and the control of HIV-1 in humans.” PLoS Genet 5(12): e1000791.

    Article  PubMed  CAS  Google Scholar 

  • Fellay, J., K. V. Shianna, et al. (2007). “A whole-genome association study of major determinants for host control of HIV-1.” Science 317(5840): 944–7.

    Article  PubMed  CAS  Google Scholar 

  • Ferre, A. L., P. W. Hunt, et al. (2009). “Mucosal immune responses to HIV-1 in elite controllers: a potential correlate of immune control.” Blood 113(17): 3978–89.

    Article  PubMed  CAS  Google Scholar 

  • Ferre, A. L., P. W. Hunt, et al. (2010). “HIV controllers with HLA-DRB1*13 and HLA-DQB1*06 alleles have strong, polyfunctional mucosal CD4+ T-cell responses.” J Virol 84(21): 11020–9.

    Article  PubMed  CAS  Google Scholar 

  • Ferre, A. L., D. Lemongello, et al. (2010). “Immunodominant HIV-specific CD8+ T-cell responses are common to blood and gastrointestinal mucosa, and Gag-specific responses dominate in rectal mucosa of HIV controllers.” J Virol 84(19): 10354–65.

    Article  PubMed  CAS  Google Scholar 

  • Feuerer, M., J. A. Hill, et al. (2009). “Foxp3+ regulatory T cells: differentiation, specification, subphenotypes.” Nat Immunol 10(7): 689–95.

    Article  PubMed  CAS  Google Scholar 

  • Franchini, G., J. Nacsa, et al. (2002). “Immune intervention strategies for HIV-1 infection of humans in the SIV macaque model.” Vaccine 20 Suppl 4: A52-60.

    Article  PubMed  CAS  Google Scholar 

  • Franchini, G., M. Robert-Guroff, et al. (1986). “Cytoplasmic localization of the HTLV-III 3′ orf protein in cultured T cells.” Virology 155(2): 593–9.

    Article  PubMed  CAS  Google Scholar 

  • Freed, E. O. and M. A. Martin (2007). HIVs and Their Replication. Fields Virology. D. Knipe and P. M. Howley. Philadelphia, PA, Lippincott Williams & Wilkins. 2: 21072186.

    Google Scholar 

  • Freel, S. A., L. Lamoreaux, et al. (2010). “Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination.” J Virol 84(10): 4998–5006.

    Article  PubMed  CAS  Google Scholar 

  • Freel, S. A., K. O. Saunders, et al. (2011). “CD8(+)T-cell-mediated control of HIV-1 and SIV infection.” Immunol Res 49(1–3): 135–46.

    Article  PubMed  CAS  Google Scholar 

  • Freeman, G. J., E. J. Wherry, et al. (2006). “Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade.” J Exp Med 203(10): 2223–7.

    Article  PubMed  CAS  Google Scholar 

  • Frost, S. D., A. Trkola, et al. (2008). “Antibody responses in primary HIV-1 infection.” Curr Opin HIV AIDS 3(1): 45–51.

    Article  PubMed  Google Scholar 

  • Frost, S. D., T. Wrin, et al. (2005). “Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection.” Proc Natl Acad Sci USA 102(51): 18514–9.

    Article  PubMed  CAS  Google Scholar 

  • Gao, X., G. W. Nelson, et al. (2001). “Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS.” N Engl J Med 344(22): 1668–75.

    Article  PubMed  CAS  Google Scholar 

  • Gillespie, G. M., A. Bashirova, et al. (2007). “Lack of KIR3DS1 binding to MHC class I Bw4 tetramers in complex with CD8+ T cell epitopes.” AIDS Res Hum Retroviruses 23(3): 451–5.

    Article  PubMed  CAS  Google Scholar 

  • Gilliam, B. L., D. J. Riedel, et al. (2011). “Clinical use of CCR5 inhibitors in HIV and beyond.” J Transl Med 9 Suppl 1: S9.

    Article  PubMed  CAS  Google Scholar 

  • Giraldo-Vela, J. P., R. Rudersdorf, et al. (2008). “The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.” J Virol 82(2): 859–70.

    Article  PubMed  CAS  Google Scholar 

  • Goffinet, C., N. Michel, et al. (2007). “Primary T-cells from human CD4/CCR5-transgenic rats support all early steps of HIV-1 replication including integration, but display impaired viral gene expression.” Retrovirology 4: 53.

    Article  PubMed  CAS  Google Scholar 

  • Gordon, S. N., B. Cervasi, et al. (2010). “Disruption of intestinal CD4+ T cell homeostasis is a key marker of systemic CD4+ T cell activation in HIV-infected individuals.” J immunol 185(9): 5169–79.

    Article  PubMed  CAS  Google Scholar 

  • Gordon, S. N., N. R. Klatt, et al. (2007). “Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys.” J immunol 179(5): 3026–34.

    PubMed  CAS  Google Scholar 

  • Gosselin, A., P. Monteiro, et al. (2010). “Peripheral blood CCR4  +  CCR6+ and CXCR3  +  CCR6  +  CD4+ T cells are highly permissive to HIV-1 infection.” J immunol 184(3): 1604–16.

    Article  PubMed  CAS  Google Scholar 

  • Goulder, P. J. and D. I. Watkins (2004). “HIV and SIV CTL escape: implications for vaccine design.” Nat Rev Immunol 4(8): 630–40.

    Article  PubMed  CAS  Google Scholar 

  • Haase, A. T. (2010). “Targeting early infection to prevent HIV-1 mucosal transmission.” Nature 464(7286): 217–23.

    Article  PubMed  CAS  Google Scholar 

  • Hahn, B. H., G. M. Shaw, et al. (2000). “AIDS as a zoonosis: scientific and public health ­implications.” Science 287(5453): 607–14.

    Article  PubMed  CAS  Google Scholar 

  • Hansen, S. G., C. Vieville, et al. (2009). “Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge.” Nat Med 15(3): 293–9.

    Article  PubMed  CAS  Google Scholar 

  • Herbeuval, J. P., A. W. Hardy, et al. (2005). “Regulation of TNF-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: role of type I IFN-producing plasmacytoid dendritic cells.” Proc Natl Acad Sci USA 102(39): 13974–9.

    Article  PubMed  CAS  Google Scholar 

  • Herbeuval, J. P., J. Nilsson, et al. (2009). “HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques.” AIDS 23(1): 35–40.

    Article  PubMed  CAS  Google Scholar 

  • Hersperger, A. R., J. N. Martin, et al. (2011). “Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression.” Blood.

    Google Scholar 

  • Hersperger, A. R., F. Pereyra, et al. (2010). “Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control.” PLoS Pathog 6(5): e1000917.

    Article  PubMed  CAS  Google Scholar 

  • Hofer, U., E. Schlaepfer, et al. (2010). “Inadequate clearance of translocated bacterial products in HIV-infected humanized mice.” PLoS Pathog 6(4): e1000867.

    Article  PubMed  CAS  Google Scholar 

  • Hryniewicz, A., A. Boasso, et al. (2006). “CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques.” Blood 108(12): 3834–42.

    Article  PubMed  CAS  Google Scholar 

  • Hu, J., M. B. Gardner, et al. (2000). “Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells.” J Virol 74(13): 6087–95.

    Article  PubMed  CAS  Google Scholar 

  • Huang, J., J. J. Goedert, et al. (2009). “HLA-B*35-Px-mediated acceleration of HIV-1 infection by increased inhibitory immunoregulatory impulses.” J Exp Med 206(13): 2959–66.

    Article  PubMed  CAS  Google Scholar 

  • Hunt, P. W. (2007). “Role of immune activation in HIV pathogenesis.” Curr HIV/AIDS Rep 4(1): 42–7.

    Article  PubMed  Google Scholar 

  • Huseby, E. S., J. White, et al. (2005). “How the T cell repertoire becomes peptide and MHC specific.” Cell 122(2): 247–60.

    Article  PubMed  CAS  Google Scholar 

  • Jacks, T., M. D. Power, et al. (1988). “Characterization of ribosomal frameshifting in HIV-1 gag-pol expression.” Nature 331(6153): 280–3.

    Article  PubMed  CAS  Google Scholar 

  • Jin, X., D. E. Bauer, et al. (1999). “Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques.” J Exp Med 189(6): 991–8.

    Article  PubMed  CAS  Google Scholar 

  • Jones, R. B., L. C. Ndhlovu, et al. (2008). “Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection.” J Exp Med 205(12): 2763–79.

    Article  PubMed  CAS  Google Scholar 

  • Josefowicz, S. Z. and A. Rudensky (2009). “Control of regulatory T cell lineage commitment and maintenance.” Immunity 30(5): 616–25.

    Article  PubMed  CAS  Google Scholar 

  • Julg, B., E. S. Moodley, et al. (2011). “Possession of HLA Class II DRB1*1303 Associates with Reduced Viral Loads in Chronic HIV-1 Clade C and B Infection.” J Infect Dis 203(6): 803–9.

    Article  PubMed  CAS  Google Scholar 

  • Kalams, S. A., P. J. Goulder, et al. (1999). “Levels of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte effector and memory responses decline after suppression of viremia with highly active antiretroviral therapy.” J Virol 73(8): 6721–8.

    PubMed  CAS  Google Scholar 

  • Kassu, A., R. A. Marcus, et al. (2010). “Suppression of HIV replication by antiretroviral therapy reduces TIM-3 expression on HIV-specific CD8(+) T cells.” AIDS Res Hum Retroviruses 27(1): 1–3.

    Article  PubMed  Google Scholar 

  • Kaufmann, D. E., D. G. Kavanagh, et al. (2007). “Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction.” Nat Immunol 8(11): 1246–54.

    Article  PubMed  CAS  Google Scholar 

  • Keele, B. F., E. E. Giorgi, et al. (2008). “Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.” Proc Natl Acad Sci USA 105(21): 7552–7.

    Article  PubMed  CAS  Google Scholar 

  • Kiepiela, P., A. J. Leslie, et al. (2004). “Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA.” Nature 432(7018): 769–75.

    Article  PubMed  CAS  Google Scholar 

  • Killian, M. S., C. Johnson, et al. (2011). “Natural suppression of human immunodeficiency virus type 1 replication is mediated by transitional memory CD8+ T cells.” J Virol 85(4): 1696–705.

    Article  PubMed  CAS  Google Scholar 

  • Kinloch-de Loes, S., B. Hoen, et al. (2005). “Impact of therapeutic immunization on HIV-1 ­viremia after discontinuation of antiretroviral therapy initiated during acute infection.” J Infect Dis 192(4): 607–17.

    Article  PubMed  CAS  Google Scholar 

  • Kinter, A., J. McNally, et al. (2007). “Suppression of HIV-specific T cell activity by lymph node CD25+ regulatory T cells from HIV-infected individuals.” Proc Natl Acad Sci USA 104(9): 3390–5.

    Article  PubMed  CAS  Google Scholar 

  • Kolte, L., J. C. Gaardbo, et al. (2009). “Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs.” Clin Exp Immunol 155(1): 44–52.

    Article  PubMed  CAS  Google Scholar 

  • Korn, T., E. Bettelli, et al. (2009). “IL-17 and Th17 Cells.” Annu Rev Immunol 27: 485–517.

    Article  PubMed  CAS  Google Scholar 

  • Kornfeld, C., M. J. Ploquin, et al. (2005). “Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS.” J Clin Invest 115(4): 1082–91.

    PubMed  CAS  Google Scholar 

  • Kosmrlj, A., E. L. Read, et al. (2010). “Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection.” Nature 465(7296): 350–4.

    Article  PubMed  CAS  Google Scholar 

  • Koup, R. A., J. T. Safrit, et al. (1994). “Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.” J Virol 68(7): 4650–5.

    PubMed  CAS  Google Scholar 

  • Kramer, R. A., M. D. Schaber, et al. (1986). “HTLV-III gag protein is processed in yeast cells by the virus pol-protease.” Science 231(4745): 1580–4.

    Article  PubMed  CAS  Google Scholar 

  • Kuritzkes, D. R. and B. D. Walker (2007). HIV-1 Pathogenesis, Clinical Manifestations and Treatment. Fields Virology. D. Knipe and P. M. Howley. Philadelphia, PA, Lippincott Williams & Wilkins. 2: 21872214.

    Google Scholar 

  • Laforge, M., F. Petit, et al. (2007). “Commitment to apoptosis in CD4(+) T lymphocytes productively infected with human immunodeficiency virus type 1 is initiated by lysosomal membrane permeabilization, itself induced by the isolated expression of the viral protein Nef.” J Virol 81(20): 11426–40.

    Article  PubMed  CAS  Google Scholar 

  • Lederman, M. M. (2001). “Immune restoration and CD4+ T-cell function with antiretroviral therapies.” AIDS 15 Suppl 2: S11-5.

    Article  PubMed  CAS  Google Scholar 

  • Legrand, F. A., D. F. Nixon, et al. (2006). “Strong HIV-1-specific T cell responses in HIV-1-exposed uninfected infants and neonates revealed after regulatory T cell removal.” PLoS One 1: e102.

    Article  PubMed  CAS  Google Scholar 

  • Legrand, N., A. Ploss, et al. (2009). “Humanized mice for modeling human infectious disease: challenges, progress, and outlook.” Cell Host Microbe 6(1): 5–9.

    Article  PubMed  CAS  Google Scholar 

  • Leslie, A. J., K. J. Pfafferott, et al. (2004). “HIV evolution: CTL escape mutation and reversion after transmission.” Nat Med 10(3): 282–9.

    Article  PubMed  CAS  Google Scholar 

  • Letvin, N. L., J. R. Mascola, et al. (2006). “Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys.” Science 312(5779): 1530–3.

    Article  PubMed  CAS  Google Scholar 

  • Levesque, M. C., M. A. Moody, et al. (2009). “Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.” PLoS Med 6(7): e1000107.

    Article  PubMed  CAS  Google Scholar 

  • Levy, J. A. (2007). HIV and the Pathogenesis of AIDS. Washington, D.C., ASM Press.

    Google Scholar 

  • Levy, Y., C. Lacabaratz, et al. (2009). “Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment.” J Clin Invest 119(4): 997–1007.

    PubMed  CAS  Google Scholar 

  • Li, Q., L. Duan, et al. (2005). “Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells.” Nature 434(7037): 1148–52.

    PubMed  CAS  Google Scholar 

  • Li, Q., P. J. Skinner, et al. (2009). “Visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection.” Science 323(5922): 1726–9.

    Article  PubMed  CAS  Google Scholar 

  • Li, S., E. J. Gowans, et al. (2008). “Natural regulatory T cells and persistent viral infection.” J Virol 82(1): 21–30.

    Article  PubMed  CAS  Google Scholar 

  • Lichterfeld, M., D. E. Kaufmann, et al. (2004). “Loss of HIV-1-specific CD8+ T cell proliferation after acute HIV-1 infection and restoration by vaccine-induced HIV-1-specific CD4+ T cells.” J Exp Med 200(6): 701–12.

    Article  PubMed  CAS  Google Scholar 

  • Lifson, J. D., M. B. Feinberg, et al. (1986). “Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein.” Nature 323(6090): 725–8.

    Article  PubMed  CAS  Google Scholar 

  • Lim, A., D. Tan, et al. (2007). “Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high on antiretroviral therapy.” AIDS 21(12): 1525–34.

    Article  PubMed  Google Scholar 

  • Liu, J., N. Gong, et al. (2009). “Neuromodulatory activities of CD4  +  CD25+ regulatory T cells in a murine model of HIV-1-associated neurodegeneration.” J Immunol 182(6): 3855–65.

    Article  PubMed  CAS  Google Scholar 

  • Liu, J., B. F. Keele, et al. (2010). “Low-dose mucosal simian immunodeficiency virus infection restricts early replication kinetics and transmitted virus variants in rhesus monkeys.” J Virol 84(19): 10406–12.

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Herrera, A., Y. Liu, et al. (2005). “HIV-1 interaction with human mannose receptor (hMR) induces production of matrix metalloproteinase 2 (MMP-2) through hMR-mediated intracellular signaling in astrocytes.” Biochim Biophys Acta 1741(1–2): 55–64.

    PubMed  CAS  Google Scholar 

  • Macal, M., S. Sankaran, et al. (2008). “Effective CD4+ T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses.” Mucosal Immunol 1(6): 475–88.

    Article  PubMed  CAS  Google Scholar 

  • Maecker, H. T. (2009). “Multiparameter flow cytometry monitoring of T cell responses.” Methods Mol Biol 485: 375–91.

    Article  PubMed  CAS  Google Scholar 

  • Maggi, E., M. Mazzetti, et al. (1994). “Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells.” Science 265(5169): 244–8.

    Article  PubMed  CAS  Google Scholar 

  • Makedonas, G. and M. R. Betts (2011). “Living in a house of cards: re-evaluating CD8+ T-cell immune correlates against HIV.” Immunol Rev 239(1): 109–24.

    Article  PubMed  CAS  Google Scholar 

  • Malhotra, U., S. Holte, et al. (2001). “Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment.” J Clin Invest 107(4): 505–17.

    Article  PubMed  CAS  Google Scholar 

  • Malim, M. H., J. Hauber, et al. (1989). “The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA.” Nature 338(6212): 254–7.

    Article  PubMed  CAS  Google Scholar 

  • Manches, O., D. Munn, et al. (2008). “HIV-activated human plasmacytoid DCs induce Tregs through an indoleamine 2,3-dioxygenase-dependent mechanism.” J Clin Invest 118(10): 3431–9.

    Article  PubMed  CAS  Google Scholar 

  • Martin, M. P., Y. Qi, et al. (2007). “Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1.” Nat Genet 39(6): 733–40.

    Article  PubMed  CAS  Google Scholar 

  • Mattapallil, J. J., D. C. Douek, et al. (2005). “Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection.” Nature 434(7037): 1093–7.

    Article  PubMed  CAS  Google Scholar 

  • McCune, J. M., M. B. Hanley, et al. (2000). “Factors influencing T-cell turnover in HIV-1-seropositive patients.” J Clin Invest 105(5): R1-8.

    Article  PubMed  CAS  Google Scholar 

  • McMichael, A. J. and C. A. O’Callaghan (1998). “A new look at T cells.” J Exp Med 187(9): 1367–71.

    Article  PubMed  CAS  Google Scholar 

  • Mehandru, S., M. A. Poles, et al. (2004). “Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract.” J Exp Med 200(6): 761–70.

    Article  PubMed  CAS  Google Scholar 

  • Mellors, J. W., A. Munoz, et al. (1997). “Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection.” Ann Intern Med 126(12): 946–54.

    PubMed  CAS  Google Scholar 

  • Mellors, J. W., C. R. Rinaldo, Jr., et al. (1996). “Prognosis in HIV-1 infection predicted by the quantity of virus in plasma [see comments] [published erratum appears in Science 1997 Jan 3;275(5296):14].” Science 272(5265): 1167–70.

    Article  PubMed  CAS  Google Scholar 

  • Michel, N., C. Goffinet, et al. (2009). “Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivo.” Retrovirology 6: 2.

    Article  PubMed  CAS  Google Scholar 

  • Miedema, F., L. Meyaard, et al. (1994). “Changing virus-host interactions in the course of HIV-1 infection.” Immunol Rev 140: 35–72.

    Article  PubMed  CAS  Google Scholar 

  • Migueles, S. A., A. C. Laborico, et al. (2002). “HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors.” Nat Immunol 3(11): 1061–8.

    Article  PubMed  CAS  Google Scholar 

  • Migueles, S. A., C. M. Osborne, et al. (2008). “Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control.” Immunity 29(6): 1009–21.

    Article  PubMed  CAS  Google Scholar 

  • Mikovits, J. A., D. D. Taub, et al. (1998). “Similar levels of human immunodeficiency virus type 1 replication in human TH1 and TH2 clones.” J Virol 72(6): 5231–8.

    PubMed  CAS  Google Scholar 

  • Mildvan, D., U. Mathur, et al. (1982). “Opportunistic infections and immune deficiency in homosexual men.” Ann Intern Med 96(6 Pt 1): 700–4.

    PubMed  CAS  Google Scholar 

  • Milush, J. M., J. D. Reeves, et al. (2007). “Virally induced CD4+ T cell depletion is not sufficient to induce AIDS in a natural host.” J immunol 179(5): 3047–56.

    PubMed  CAS  Google Scholar 

  • Miura, T., M. A. Brockman, et al. (2009). “HLA-associated alterations in replication capacity of chimeric NL4-3 viruses carrying gag-protease from elite controllers of human immunodeficiency virus type 1.” J Virol 83(1): 140–9.

    Article  PubMed  CAS  Google Scholar 

  • Miura, T., M. A. Brockman, et al. (2009). “HLA-B57/B*5801 human immunodeficiency virus type 1 elite controllers select for rare gag variants associated with reduced viral replication capacity and strong cytotoxic T-lymphocyte [corrected] recognition.” J Virol 83(6): 2743–55.

    Article  PubMed  CAS  Google Scholar 

  • Montes, M., C. Sanchez, et al. (2011). “Normalization of FoxP3(+) regulatory T cells in response to effective antiretroviral therapy.” J Infect Dis 203(4): 496–9.

    Article  PubMed  CAS  Google Scholar 

  • Moonis, M., B. Lee, et al. (2001). “CCR5 and CXCR4 expression correlated with X4 and R5 HIV-1 infection yet not sustained replication in Th1 and Th2 cells.” AIDS 15(15): 1941–9.

    Article  PubMed  CAS  Google Scholar 

  • Moreno-Fernandez, M. E., C. Rueda, et al. (2011). “Regulatory T cells control HIV replication in activated T cells through a cAMP-dependent mechanism.” Blood 117(20): 5372–80.

    Google Scholar 

  • Moreno-Fernandez, M. E., W. Zapata, et al. (2009). “Human Regulatory T Cells Are Targets for Human Immunodeficiency Virus (HIV) Infection, and Their Susceptibility Differs Depending on the HIV Type 1 Strain.” J Virol 83(24): 12925–12933.

    Article  PubMed  CAS  Google Scholar 

  • Ndhlovu, L. C., C. P. Loo, et al. (2008). “FOXP3 expressing CD127lo CD4+ T cells inversely ­correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection.” J Leukoc Biol 83(2): 254–62.

    Article  PubMed  CAS  Google Scholar 

  • Neil, S. and P. Bieniasz (2009). “Human immunodeficiency virus, restriction factors, and interferon.” J Interferon Cytokine Res 29(9): 569–80.

    Article  PubMed  CAS  Google Scholar 

  • Nilsson, J., A. Boasso, et al. (2006). “HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS.” Blood 108(12): 3808–17.

    Article  PubMed  CAS  Google Scholar 

  • Nyakeriga, A. M., C. J. Fichtenbaum, et al. (2009). “Engagement of the CD4 receptor affects the redistribution of Lck to the immunological synapse in primary T cells: implications for T-cell activation during human immunodeficiency virus type 1 infection.” J Virol 83(3): 1193–200.

    Article  PubMed  CAS  Google Scholar 

  • Oberlin, E., A. Amara, et al. (1996). “The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1.” Nature 382(6594): 833–5.

    Article  PubMed  CAS  Google Scholar 

  • Ogg, G. S., X. Jin, et al. (1999). “Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy.” J Virol 73(1): 797–800.

    PubMed  CAS  Google Scholar 

  • Ortiz, G. M., M. Wellons, et al. (2001). “Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects.” Proc Natl Acad Sci USA 98(23): 13288–93.

    Article  PubMed  CAS  Google Scholar 

  • Oyaizu, N., Y. Adachi, et al. (1997). “Monocytes express Fas ligand upon CD4 cross-linking and induce CD4+ T cells apoptosis: a possible mechanism of bystander cell death in HIV infection.” J immunol 158(5): 2456–63.

    PubMed  CAS  Google Scholar 

  • Palmer, B. E., E. Boritz, et al. (2004). “Effects of sustained HIV-1 plasma viremia on HIV-1 Gag-specific CD4+ T cell maturation and function.” J immunol 172(5): 3337–47.

    PubMed  CAS  Google Scholar 

  • Pandrea, I., G. Silvestri, et al. (2009). “AIDS in african nonhuman primate hosts of SIVs: a new paradigm of SIV infection.” Curr HIV Res 7(1): 57–72.

    Article  PubMed  CAS  Google Scholar 

  • Pandrea, I. V., R. Gautam, et al. (2007). “Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence.” J immunol 179(5): 3035–46.

    PubMed  CAS  Google Scholar 

  • Pelak, K., D. B. Goldstein, et al. (2010). “Host determinants of HIV-1 control in African Americans.” J Infect Dis 201(8): 1141–9.

    Article  PubMed  CAS  Google Scholar 

  • Pereyra, F., X. Jia, et al. (2010). “The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.” Science 330(6010): 1551–7.

    Article  PubMed  CAS  Google Scholar 

  • Petrovas, C., J. P. Casazza, et al. (2006). “PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection.” J Exp Med 203(10): 2281–92.

    Article  PubMed  CAS  Google Scholar 

  • Qi, Y., M. P. Martin, et al. (2006). “KIR/HLA pleiotropism: protection against both HIV and opportunistic infections.” PLoS Pathog 2(8): e79.

    Article  PubMed  CAS  Google Scholar 

  • Qin, S., Y. Sui, et al. (2008). “Chemokine and cytokine mediated loss of regulatory T cells in lymph nodes during pathogenic simian immunodeficiency virus infection.” J immunol 180(8): 5530–6.

    PubMed  CAS  Google Scholar 

  • Raffatellu, M., R. L. Santos, et al. (2008). “Simian immunodeficiency virus-induced mucosal ­interleukin-17 deficiency promotes Salmonella dissemination from the gut.” Nat Med 14(4): 421–8.

    Article  PubMed  CAS  Google Scholar 

  • Reynolds, M. R., E. Rakasz, et al. (2005). “CD8+ T-lymphocyte response to major immunodominant epitopes after vaginal exposure to simian immunodeficiency virus: too late and too little.” J Virol 79(14): 9228–35.

    Article  PubMed  CAS  Google Scholar 

  • Reynolds, M. R., A. M. Weiler, et al. (2010). “Macaques vaccinated with simian immunodeficiency virus SIVmac239Delta nef delay acquisition and control replication after repeated low-dose heterologous SIV challenge.” J Virol 84(18): 9190–9.

    Article  PubMed  CAS  Google Scholar 

  • Rinaldo, C. R. (2009). “Dendritic cell-based human immunodeficiency virus vaccine.” J Intern Med 265(1): 138–58.

    Article  PubMed  CAS  Google Scholar 

  • Rinaldo, C. R., Jr., J. M. Liebmann, et al. (1999). “Prolonged suppression of human immunodeficiency virus type 1 (HIV-1) viremia in persons with advanced disease results in enhancement of CD4 T cell reactivity to microbial antigens but not to HIV-1 antigens.” J Infect Dis 179(2): 329–36.

    Article  PubMed  Google Scholar 

  • Robbins, G. K., J. G. Spritzler, et al. (2009). “Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group protocol 384.” Clin Infect Dis 48(3): 350–61.

    Article  PubMed  Google Scholar 

  • Rosenberg, E. S., M. Altfeld, et al. (2000). “Immune control of HIV-1 after early treatment of acute infection.” Nature 407: 523–6.

    Article  PubMed  CAS  Google Scholar 

  • Sattentau, Q. J. and R. A. Weiss (1988). “The CD4 antigen: physiological ligand and HIV receptor.” Cell 52(5): 631–3.

    Article  PubMed  CAS  Google Scholar 

  • Schacker, T. W., C. Reilly, et al. (2005). “Amount of lymphatic tissue fibrosis in HIV infection predicts magnitude of HAART-associated change in peripheral CD4 cell count.” AIDS 19(18): 2169–71.

    Article  PubMed  Google Scholar 

  • Schmitz, J. E., M. J. Kuroda, et al. (1999). “Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes.” Science 283(5403): 857–60.

    Article  PubMed  CAS  Google Scholar 

  • Schneidewind, A., M. A. Brockman, et al. (2008). “Structural and functional constraints limit options for cytotoxic T-lymphocyte escape in the immunodominant HLA-B27-restricted epitope in human immunodeficiency virus type 1 capsid.” J Virol 82(11): 5594–605.

    Article  PubMed  CAS  Google Scholar 

  • Schneidewind, A., M. A. Brockman, et al. (2007). “Escape from the dominant HLA-B27-restricted cytotoxic T-lymphocyte response in Gag is associated with a dramatic reduction in human immunodeficiency virus type 1 replication.” J Virol 81(22): 12382–93.

    Article  PubMed  CAS  Google Scholar 

  • Schweneker, M., D. Favre, et al. (2008). “HIV-induced changes in T cell signaling pathways.” J Immunol 180(10): 6490–500.

    PubMed  CAS  Google Scholar 

  • Selby, M. J., E. S. Bain, et al. (1989). “Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat.” Genes Dev 3(4): 547–58.

    Article  PubMed  CAS  Google Scholar 

  • Shearer, G. M. (1998). “HIV-induced immunopathogenesis.” Immunity 9: 587–93.

    Article  PubMed  CAS  Google Scholar 

  • Shearer, G. M., E. Roilides, et al. (1991). “CD4+ T helper cell function is actively suppressed in HIV infection.” Int Conf Aids 7(1).

    Google Scholar 

  • Sodora, D. L., J. S. Allan, et al. (2009). “Toward an AIDS vaccine: lessons from natural simian immunodeficiency virus infections of African nonhuman primate hosts.” Nat Med 15(8): 861–5.

    Article  PubMed  CAS  Google Scholar 

  • Sodroski, J., W. C. Goh, et al. (1986). “A second post-transcriptional trans-activator gene required for HTLV-III replication.” Nature 321(6068): 412–7.

    Article  PubMed  CAS  Google Scholar 

  • Spiegel, H. M., E. DeFalcon, et al. (1999). “Changes in frequency of HIV-1-specific cytotoxic T cell precursors and circulating effectors after combination antiretroviral therapy in children.” J Infect Dis 180(2): 359–68.

    Article  PubMed  CAS  Google Scholar 

  • Stamatatos, L., L. Morris, et al. (2009). “Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine?” Nat Med 15(8): 866–70.

    PubMed  CAS  Google Scholar 

  • Starcich, B., L. Ratner, et al. (1985). “Characterization of long terminal repeat sequences of HTLV-III.” Science 227(4686): 538–40.

    Article  PubMed  CAS  Google Scholar 

  • Sterne, J. A., M. May, et al. (2009). “Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies.” Lancet 373(9672): 1352–63.

    Article  PubMed  CAS  Google Scholar 

  • Strebel, K., D. Daugherty, et al. (1987). “The HIV ‘A’ (sor) gene product is essential for virus infectivity.” Nature 328(6132): 728–30.

    Article  PubMed  CAS  Google Scholar 

  • Strebel, K., T. Klimkait, et al. (1988). “A novel gene of HIV-1, vpu, and its 16-kilodalton product.” Science 241(4870): 1221–3.

    Article  PubMed  CAS  Google Scholar 

  • Strebel, K., J. Luban, et al. (2009). “Human cellular restriction factors that target HIV-1 replication.” BMC Med 7: 48.

    Article  PubMed  CAS  Google Scholar 

  • Streeck, H., Z. L. Brumme, et al. (2008). “Antigen load and viral sequence diversification determine the functional profile of HIV-1-specific CD8+ T cells.” PLoS Med 5(5): e100.

    Article  PubMed  CAS  Google Scholar 

  • Streeck, H., J. S. Jolin, et al. (2009). “Human immunodeficiency virus type 1-specific CD8+ T-cell responses during primary infection are major determinants of the viral set point and loss of CD4+ T cells.” J Virol 83(15): 7641–8.

    Article  PubMed  CAS  Google Scholar 

  • Streeck, H., M. Lichterfeld, et al. (2007). “Recognition of a defined region within p24 gag by CD8+ T cells during primary human immunodeficiency virus type 1 infection in individuals expressing protective HLA class I alleles.” J Virol 81(14): 7725–31.

    Article  PubMed  CAS  Google Scholar 

  • Sun, Y., J. E. Schmitz, et al. (2005). “Dysfunction of simian immunodeficiency virus/simian human immunodeficiency virus-induced IL-2 expression by central memory CD4+ T lymphocytes.” J immunol 174(8): 4753–60.

    PubMed  CAS  Google Scholar 

  • Tamma, S. M., N. Chirmule, et al. (1997). “Signals transduced through the CD4 molecule interfere with TCR/CD3-mediated ras activation leading to T cell anergy/apoptosis.” Clin Immunol Immunopathol 85(2): 195–201.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka, Y., Y. Koyanagi, et al. (1997). “Productive and lytic infection of human CD4+ type 1 helper T cells with macrophage-tropic human immunodeficiency virus type 1.” J Virol 71(1): 465–70.

    PubMed  CAS  Google Scholar 

  • Teleshova, N., I. Frank, et al. (2003). “Immunodeficiency virus exploitation of dendritic cells in the early steps of infection.” J Leukoc Biol 74(5): 683–90.

    Article  PubMed  CAS  Google Scholar 

  • Tervo, H. M., C. Goffinet, et al. (2008). “Mouse T-cells restrict replication of human immunodeficiency virus at the level of integration.” Retrovirology 5: 58.

    PubMed  Google Scholar 

  • Terwilliger, E., J. G. Sodroski, et al. (1986). “Effects of mutations within the 3′ orf open reading frame region of human T-cell lymphotropic virus type III (HTLV-III/LAV) on replication and cytopathogenicity.” J Virol 60(2): 754–60.

    PubMed  CAS  Google Scholar 

  • Thorborn, G., L. Pomeroy, et al. (2010). “Increased sensitivity of CD4+ T-effector cells to CD4  +  CD25+ Treg suppression compensates for reduced Treg number in asymptomatic HIV-1 infection.” PLoS ONE 5(2): e9254.

    Article  PubMed  CAS  Google Scholar 

  • Thoulouze, M. I., N. Sol-Foulon, et al. (2006). “Human immunodeficiency virus type-1 infection impairs the formation of the immunological synapse.” Immunity 24(5): 547–61.

    Article  PubMed  CAS  Google Scholar 

  • Trautmann, L., L. Janbazian, et al. (2006). “Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction.” Nat Med 12(10): 1198–202.

    Article  PubMed  CAS  Google Scholar 

  • Van Duyne, R., C. Pedati, et al. (2009). “The utilization of humanized mouse models for the study of human retroviral infections.” Retrovirology 6: 76.

    Article  PubMed  CAS  Google Scholar 

  • Veazey, R. S., M. DeMaria, et al. (1998). “Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection.” Science 280(5362): 427–31.

    Article  PubMed  CAS  Google Scholar 

  • Velilla, P. A., M. T. Shata, et al. (2008). “Effect of Low-Dose IL-2 Immunotherapy on Frequency and Phenotype of Regulatory T cells and NK Cells in HIV/HCV-coinfected Patients.” AIDS Res Hum Retroviruses 24(1): 52–61.

    Article  PubMed  CAS  Google Scholar 

  • Velu, V., K. Titanji, et al. (2009). “Enhancing SIV-specific immunity in vivo by PD-1 blockade.” Nature 458(7235): 206–10.

    Article  PubMed  CAS  Google Scholar 

  • Veronese, F. D., A. L. DeVico, et al. (1985). “Characterization of gp41 as the transmembrane protein coded by the HTLV-III/LAV envelope gene.” Science 229(4720): 1402–5.

    Article  PubMed  CAS  Google Scholar 

  • Vetter, M. L., M. E. Johnson, et al. (2009). “Differences in APOBEC3G expression in CD4+ T helper lymphocyte subtypes modulate HIV-1 infectivity.” PLoS Pathog 5(2): e1000292.

    Article  PubMed  CAS  Google Scholar 

  • Vingert, B., S. Perez-Patrigeon, et al. (2010). “HIV controller CD4+ T cells respond to minimal amounts of Gag antigen due to high TCR avidity.” PLoS Pathog 6(2): e1000780.

    Article  PubMed  CAS  Google Scholar 

  • Weiss, L., V. Donkova-Petrini, et al. (2004). “Human immunodeficiency virus-driven expansion of CD4  +  CD25+ Regulatory T cells Which Suppress HIV-specific CD4 T-cell Responses in HIV-infected Patients.” Blood 104: 3249–56.

    Article  PubMed  CAS  Google Scholar 

  • Weiss, L., F. A. Letimier, et al. (2010). “In vivo expansion of naive and activated CD4  +  CD25  +  FOXP3+ regulatory T cell populations in interleukin-2-treated HIV patients.” Proc Natl Acad Sci USA 107(23): 10632–7.

    Article  PubMed  CAS  Google Scholar 

  • Wherry, E. J. and R. Ahmed (2004). “Memory CD8 T-cell differentiation during viral infection.” J Virol 78(11): 5535–45.

    Article  PubMed  CAS  Google Scholar 

  • Wherry, E. J., J. N. Blattman, et al. (2003). “Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment.” J Virol 77(8): 4911–27.

    Article  PubMed  CAS  Google Scholar 

  • Wherry, E. J., S. J. Ha, et al. (2007). “Molecular signature of CD8+ T cell exhaustion during chronic viral infection.” Immunity 27(4): 670–84.

    Article  PubMed  CAS  Google Scholar 

  • Wu, L. and V. N. KewalRamani (2006). “Dendritic-cell interactions with HIV: infection and viral dissemination.” Nat Rev Immunol 6(11): 859–68.

    Article  PubMed  CAS  Google Scholar 

  • Xiao, P., O. Usami, et al. (2008). “Characterization of a CD4-independent clinical HIV-1 that can efficiently infect human hepatocytes through chemokine (C-X-C motif) receptor 4.” AIDS 22(14): 1749–57.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, R., C. Fichtenbaum, et al. (2004). “CD40 Ligand dysregulation in HIV infection: HIV gp120 inhibits signaling cascades upstream of CD40 Ligand transcription.” J Immunol 172: 2678–2686.

    PubMed  CAS  Google Scholar 

  • Zhang, Z., T. Schuler, et al. (1999). “Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells.” Science 286(5443): 1353–7.

    Article  PubMed  CAS  Google Scholar 

  • Zolopa, A. R., D. S. Berger, et al. (2010). “Activity of elvitegravir, a once-daily integrase inhibitor, against resistant HIV Type 1: results of a phase 2, randomized, controlled, dose-ranging clinical trial.” J Infect Dis 201(6): 814–22.

    Article  PubMed  CAS  Google Scholar 

  • Zwick, M. B. and D. R. Burton (2007). “HIV-1 neutralization: mechanisms and relevance to vaccine design.” Curr HIV Res 5(6): 608–24.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the members of their laboratories and their colleagues for useful discussions, as well as their mentors without whom they would not have joined the HIV research field. CAC wants to particularly thank Dr Gene Shearer. CAC is supported by the National Institutes of Health (R01 AI068524, R01 AG033057 and U01 HL101800). BLS is supported by the National Institutes of Health (R01 AI057020, R01 DE021273, P01 AI083050, and R21 NS069219) and the American Foundation for AIDS Research (AmFAR 107854-RGRL).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Claire A. Chougnet .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media LLC

About this chapter

Cite this chapter

Chougnet, C.A., Shacklett, B.L. (2012). T Cell Responses During Human Immunodeficiency Virus (HIV)-1 Infection. In: Aliberti, J. (eds) Control of Innate and Adaptive Immune Responses during Infectious Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0484-2_8

Download citation

Publish with us

Policies and ethics