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The HIV infection and immune activation: ‘To fight and burn’

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Abstract

Immune activation, a normal immune reaction to pathogens, is now recognized as a major driving force of the CD4 T-cell depletion and immune disorders caused by HIV. By contrast, the natural hosts of its ancestor virus, simian immunodeficiency virus, have adapted to this virus by blocking immune activation and remaining healthy. This review will focus on evidence demonstrating how immune activation associated with HIV infection exhausts immune defenses to HIV as well as the immune system, thus leading to immunosenescence and immunodeficiency, and how treatment can disrupt this vicious and ultimately fatal circle.

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References

  1. Borkow G, Leng Q, Weisman Z, et al.: Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy. J Clin Invest 2000, 106:1053–1060.

    PubMed  CAS  Google Scholar 

  2. Giorgi JV, Hultin LE, McKeating JA, et al.: Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis 1999, 179:859–870. This article is one of the key papers that first demonstrated the link between immune activation, immunopathology and disease progression with specific emphasis on the importance of the CD38 activation marker.

    Article  PubMed  CAS  Google Scholar 

  3. Bentwich Z, Kalinkovich A, Weisman Z, Grossman Z: Immune activation in the context of HIV infection. Clin Exp Immunol 1998, 111:1–2.

    Article  PubMed  CAS  Google Scholar 

  4. McCune JM: The dynamics of CD4+ T-cell depletion in HIV disease. Nature 2001, 410:974–979.

    Article  PubMed  CAS  Google Scholar 

  5. Hazenberg MD, Otto SA, Cohen Stuart JW, et al.: Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection. Nat Med 2000, 6:1036–1042. T-cell-receptor excision circles content in healthy individuals is only indirectly related to thymic output, and in HIV-1 infection is mainly affected by immune activation. This paper is one of the first to strongly suggest that naïve CD4 T cell depletion can result from immune activation and not only from thymus atrophy.

    Article  PubMed  CAS  Google Scholar 

  6. Grossman Z, Meier-Schellersheim M, Sousa AE, et al.: CD4+ Tcell depletion in HIV infection: Are we closer to understanding the cause? Nat Med 2002, 8:319–323.

    Article  PubMed  CAS  Google Scholar 

  7. Silvestri G, Feinberg MB: Turnover of lymphocytes and conceptual paradigms in HIV infection. J Clin Invest 2003, 112:821–824.

    Article  PubMed  CAS  Google Scholar 

  8. Silvestri G, Sodora DL, Koup RA, et al.: Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 2003, 18:441–452. The authors convincingly demonstrated lack of immunopathology and lack of immune activation in SIV infection of SMs.

    Article  PubMed  CAS  Google Scholar 

  9. Monceaux V, Estaquier J, Fevrier M, et al.: Extensive apoptosis in lymphoid organs during primary SIV infection predicts rapid progression towards AIDS. AIDS 2003, 17:1585–1596.

    Article  PubMed  Google Scholar 

  10. Silvestri G, Fedanov A, Germon S, et al.: Divergent host responses during primary simian immunodeficiency virus SIVsm infection of natural sooty mangabey and nonnatural rhesus macaque hosts. J Virol 2005, 79:4043–4054.

    Article  PubMed  CAS  Google Scholar 

  11. Kornfeld C, Ploquin MJ, Pandrea I, et al.: Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. J Clin Invest 2005, 115:1082–1091. This was the first article to demonstrate that generation of Tregs may be one mechanism for lack of T-cell activation during primary infection by SIV in its natural host AGMs.

    Article  PubMed  CAS  Google Scholar 

  12. Eggena MP, Barugahare B, Jones N, et al.: Depletion of regulatory T cells in HIV infection is associated with immune activation. J Immunol 2005, 174:4407–4414.

    PubMed  CAS  Google Scholar 

  13. Bukrinsky MI, Stanwick TL, Dempsey MP, Stevenson M: Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science 1991, 254:423–427.

    Article  PubMed  CAS  Google Scholar 

  14. Fauci AS: Host factors and the pathogenesis of HIV-induced disease. Nature 1996, 384:529–534.

    Article  PubMed  CAS  Google Scholar 

  15. Douek DC, Brenchley JM, Betts MR, et al.: HIV preferentially infects HIV-specific CD4+ T cells. Nature 2002, 417:95–98.

    Article  PubMed  CAS  Google Scholar 

  16. Ameisen JC, Capron A: Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunol Today 1991, 12:102–105.

    Article  PubMed  CAS  Google Scholar 

  17. Gougeon ML, Lecoeur H, Dulioust A, et al.: Programmed cell death in peripheral lymphocytes from HIV-infected persons: increased susceptibility to apoptosis of CD4 and CD8 T cells correlates with lymphocyte activation and with disease progression. J Immunol 1996, 156:3509–3520.

    PubMed  CAS  Google Scholar 

  18. Westendorp MO, Frank R, Ochsenbauer C, et al.: Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature 1995, 375:497–500.

    Article  PubMed  CAS  Google Scholar 

  19. Sastry KJ, Marin MC, Nehete PN, et al.: Expression of human immunodeficiency virus type I tat results in down-regulation of bcl-2 and induction of apoptosis in hematopoietic cells. Oncogene 1996, 13:487–493.

    PubMed  CAS  Google Scholar 

  20. Algeciras A, Dockrell DH, Lynch DH, Paya CV: CD4 regulates susceptibility to Fas ligand- and tumor necrosis factor-mediated apoptosis. J Exp Med 1998, 187:711–720.

    Article  PubMed  CAS  Google Scholar 

  21. Algeciras-Schimnich A, Vlahakis SR, Villasis-Keever A, et al.: CCR5 mediates Fas- and caspase-8 dependent apoptosis of both uninfected and HIV infected primary human CD4 T cells. AIDS 2002, 16:1467–1478.

    Article  PubMed  CAS  Google Scholar 

  22. Zangerle R, Gallati H, Sarcletti M, et al.: Increased serum concentrations of soluble tumor necrosis factor receptors in HIV-infected individuals are associated with immune activation. J Acquir Immune Defic Syndr 1994, 7:79–85.

    PubMed  CAS  Google Scholar 

  23. Adachi Y, Oyaizu N, Than S, et al.: IL-2 rescues in vitro lymphocyte apoptosis in patients with HIV infection: correlation with its ability to block culture-induced down-modulation of Bcl-2. J Immunol 1996, 157:4184–4193.

    PubMed  CAS  Google Scholar 

  24. Hellerstein M, Hanley MB, Cesar D, et al.: Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans. Nat Med 1999, 5:83–89.

    Article  PubMed  CAS  Google Scholar 

  25. Sachsenberg N, Perelson AS, Yerly S, et al.: Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen. J Exp Med 1998, 187:1295–1303.

    Article  PubMed  CAS  Google Scholar 

  26. Fleury S, de Boer RJ, Rizzardi GP, et al.: Limited CD4+ T-cell renewal in early HIV-1 infection: Effect of highly active antiretroviral therapy. Nat Med 1998, 4:794–801.

    Article  PubMed  CAS  Google Scholar 

  27. Combadere B, Blanc C, Li T, et al.: CD4+Ki67+ lymphocytes in HIV-infected patients are effector T cells accumulated in the G1 phase of the cell cycle. Eur J Immunol 2000, 30:3598–3603.

    Article  PubMed  CAS  Google Scholar 

  28. Wolthers KC, Bea G, Wisman A, et al.: T cell telomere length in HIV-1 infection: no evidence for increased CD4+ T cell turnover. Science 1996, 274:1543–1547.

    Article  PubMed  CAS  Google Scholar 

  29. Hellerstein MK, Hoh RA, Hanley MB, et al.: Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection. J Clin Invest 2003, 112:956–966.

    Article  PubMed  CAS  Google Scholar 

  30. Galati D, Paiardini M, Cervasi B, et al.: Specific changes in the posttranslational regulation of nucleolin in lymphocytes from patients infected with human immunodeficiency virus. J Infect Dis 2003, 188:1483–1491.

    Article  PubMed  Google Scholar 

  31. Yue FY, Kovacs CM, Dimayuga RC, et al.: Preferential apoptosis of HIV-1-specific CD4+ T cells. J Immunol 2005, 174:2196–2204.

    PubMed  CAS  Google Scholar 

  32. Haynes BF, Hale LP, Weinhold KJ, et al.: Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection. J Clin Invest 1999, 103:921.

    PubMed  Google Scholar 

  33. Dion ML, Poulin JF, Bordi R, et al.: HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation. Immunity 2004, 21:757–768.

    Article  PubMed  CAS  Google Scholar 

  34. Li Q, Duan L, Estes JD, et al.: Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 2005, 434:1148–1152. This paper illustrates a mechanism for loss of resting memory CD4 T cells which, in parallel to activation-induced cell death, contributes to the accelerated consumption of naïve CD4 T cells.

    PubMed  CAS  Google Scholar 

  35. Clerici M, Stocks NI, Zajac RA, et al.: Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. Independence of CD4+ cell numbers and clinical staging. J Clin Invest 1989, 84:1892–1899.

    PubMed  CAS  Google Scholar 

  36. Fan J, Bass HZ, Fahey JL: Elevated IFN-gamma and decreased IL-2 gene expression are associated with HIV infection. J Immunol 1993, 151:5031–5040.

    PubMed  CAS  Google Scholar 

  37. Gougeon ML, Montagnier L: Apoptosis in AIDS. Science 1993, 260:1269–1270.

    Article  PubMed  CAS  Google Scholar 

  38. Migueles SA, Laborico AC, Shupert WL, et al.: HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol 2002, 3:1061–1068.

    Article  PubMed  CAS  Google Scholar 

  39. Wang EC, Moss PA, Frodsham P, et al.: CD8highCD57+ T lymphocytes in normal, healthy individuals are oligoclonal and respond to human cytomegalovirus. J Immunol 1995, 155:5046–5056.

    PubMed  CAS  Google Scholar 

  40. Gorochov G, Neumann AU, Kereveur A, et al.: Perturbation of CD4+ and CD8+ T-cell repertoires during progression to AIDS and regulation of the CD4+ repertoire during antiviral therapy. Nat Med 1998, 4:215–221.

    Article  PubMed  CAS  Google Scholar 

  41. Autran B, Carcelain G, Li TS, et al.: Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 1997, 277:112–116.

    Article  PubMed  CAS  Google Scholar 

  42. Lederman MM, Connick E, Landay A, et al.: Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315. J Infect Dis 1998, 178:70–79.

    PubMed  CAS  Google Scholar 

  43. Hazenberg MD, Hamann D, Schuitemaker H, Miedema F: T cell depletion in HIV-1 infection: how CD4+ T cells go out of stock. Nat Immunol 2000, 1:285–289.

    Article  PubMed  CAS  Google Scholar 

  44. Badley AD, Dockrell DH, Algeciras A, et al.: In vivo analysis of Fas/FasL interactions in HIV-infected patients. J Clin Invest 1998, 102:79–87.

    Article  PubMed  CAS  Google Scholar 

  45. Bucy RP, Hockett RD, Derdeyn CA, et al.: Initial increase in blood CD4(+) lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J Clin Invest 1999, 103:1391–1398.

    PubMed  CAS  Google Scholar 

  46. Andersson J, Fehniger TE, Patterson BK, et al.: Early reduction of immune activation in lymphoid tissue following highly active HIV therapy. AIDS 1998, 12:F123–129.

    Article  PubMed  CAS  Google Scholar 

  47. Ogg GS, Jin X, Bonhoeffer S, et al.: Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 1998, 279:2103–2106.

    Article  PubMed  CAS  Google Scholar 

  48. Ogg GS, Jin X, Bonhoeffer S, et al.: Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy. J Virol 1999, 73:797–800.

    PubMed  CAS  Google Scholar 

  49. Mollet L, Li TS, Samri A, et al.: Dynamics of HIV-specific CD8+ T lymphocytes with changes in viral load.The RESTIM and COMET Study Groups. J Immunol 2000, 165:1692–1704.

    PubMed  CAS  Google Scholar 

  50. Conge AM, Reynes J, Atoui N, et al.: Spontaneous in vitro antihuman immunodeficiency virus type 1 antibody secretion by peripheral blood mononuclear cells is related to disease progression in zidovudine-treated adults. J Infect Dis 1994, 170:1376–1383.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratoire d’Immunologie Cellulaire, Hôpital Pitié-Salpétrière, 47-83 Boulevard de l’Hôpital, 75634, Paris cedex 13, France

    Brigitte Autran MD, PhD

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  1. Victor Appay PhD
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  2. François Boutboul MD
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  3. Brigitte Autran MD, PhD
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Appay, V., Boutboul, F. & Autran, B. The HIV infection and immune activation: ‘To fight and burn’. Curr Infect Dis Rep 7, 473–479 (2005). https://doi.org/10.1007/s11908-005-0050-9

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  • DOI: https://doi.org/10.1007/s11908-005-0050-9

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