Encyclopedia of AIDS

Living Edition
| Editors: Thomas J. Hope, Douglas Richman, Mario Stevenson

T-Cell Homeostasis

  • Julia Drylewicz
  • Kiki Tesselaar
  • José A. M. Borghans
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9610-6_207-1


During healthy aging, CD4+ and CD8+ T-cell numbers remain relatively stable, despite a significant decline in thymus output. This T-cell homeostasis is dramatically disturbed during HIV infection, during which naive and memory CD4+ and naive CD8+ T-cell numbers gradually decline, eventually leading to increased susceptibility to opportunistic infections. In contrast, memory CD8+ T-cell numbers are significantly increased in HIV infection. Although the causes of disturbed lymphocyte homeostasis in HIV infection have been subject of much debate, there is a current consensus that the deleterious effects of chronic immune activation play a central role.

During effective combination antiretroviral therapy (cART), CD4+ T-cell numbers tend to come back to healthy control levels, albeit very slowly, while memory CD8+T-cell numbers tend to remain elevated for long periods of time. It remains unclear whether active homeostatic mechanisms kick in to reestablish lymphocyte homeostasis...


Hunt Deuterium 
This is a preview of subscription content, log in to check access


  1. Bonyhadi ML, Rabin L, Salimi S, et al. HIV induces thymus depletion in vivo. Nature. 1993;363:728–32.PubMedCrossRefGoogle Scholar
  2. Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12:1365–71.PubMedCrossRefGoogle Scholar
  3. Chakrabarti LA, Lewin SR, Zhang L, et al. Normal T-cell turnover in sooty mangabeys harboring active simian immunodeficiency virus infection. J Virol. 2000;74:1209–23.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Clark DR, de Boer R, Wolthers K, Miedema F. T cell dynamics in HIV-1 infection. Adv Immunol. 1999;73:301–27.PubMedCrossRefGoogle Scholar
  5. Clayton F, Clayton CH. Gastrointestinal pathology in HIV-infected patients. Gastroenterol Clin North Am. 1997;26:191–240.PubMedCrossRefGoogle Scholar
  6. Cooper A, García M, Petrovas C, et al. HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration. Nature. 2013;498:376–9.PubMedCrossRefGoogle Scholar
  7. de Boer R, Mohri H, Ho DD, Perelson AS. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques. J Immunol. 2003;170:2479–87.PubMedCrossRefGoogle Scholar
  8. den Braber I, Mugwagwa T, Vrisekoop N, et al. Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity. 2012;36:288–97.CrossRefGoogle Scholar
  9. Doitsh G, Galloway NLK, Geng X, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature. 2014;505:509–14.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998;396:690–5.PubMedCrossRefGoogle Scholar
  11. Douek DC, Vescio RA, Betts M, et al. Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution. Lancet. 2000;355:1875–81.PubMedCrossRefGoogle Scholar
  12. Finkel TH, Tudor-Williams G, Banda NK, Cotton MF. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nat Med. 1995;1:129–34.PubMedCrossRefGoogle Scholar
  13. 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;179:859–70.PubMedCrossRefGoogle Scholar
  14. 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;103:453–60.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 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. 2000a;6:1036–42.PubMedCrossRefGoogle Scholar
  16. Hazenberg MD, Stuart JW, Otto SA, et al. T-cell division in human immunodeficiency virus (HIV)-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART). Blood. 2000b;95:249–55.PubMedGoogle Scholar
  17. Hazenberg MD, Otto SA, de Pauw ES, et al. T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell transplantation are related to clinical events. Blood. 2002;99:3449–53.PubMedCrossRefGoogle Scholar
  18. Hazenberg MD, Otto SA, Roos MTL, et al. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS. 2003;17:1881–8.PubMedCrossRefGoogle Scholar
  19. Hazenberg MD, Otto SA, van Rossum AMC, et al. Establishment of the CD4+ T-cell pool in healthy children and untreated children infected with HIV-1. Blood. 2004;104:3513–9.PubMedCrossRefGoogle Scholar
  20. Ho DD, Neumann AU, Perelson AS, et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995;373:123–6.PubMedCrossRefGoogle Scholar
  21. Hunt P, Deeks S, Rodriguez B, et al. Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy. AIDS. 2003a;17:1907–15.PubMedCrossRefGoogle Scholar
  22. Hunt P, Martin JN, Sinclair E, et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003b;187:1534–43.PubMedCrossRefGoogle Scholar
  23. Lempicki RA, Kovacs JA, Baseler M, et al. Impact of HIV-1 infection and highly active antiretroviral therapy on the kinetics of CD4+ and CD8+ T cell turnover in HIV-infected patients. Proc Natl Acad Sci U S A. 2000;97:13778–83.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Margolick J, Munoz A, Donnenberg AD, et al. Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. The Multicenter AIDS Cohort Study. Nat Med. 1995;1:674–80.PubMedCrossRefGoogle Scholar
  25. McCune JM. The dynamics of CD4+ T-cell depletion in HIV disease. Nature. 2001;410:974–9.PubMedCrossRefGoogle Scholar
  26. Meier A, Alter G, Frahm N, et al. MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands. J Virol. 2007;81:8180–91.PubMedCrossRefPubMedCentralGoogle Scholar
  27. Meyaard L, Otto SA, Jonker RR, et al. Programmed death of T cells in HIV-1 infection. Science. 1992;257:217–9.PubMedCrossRefGoogle Scholar
  28. Miedema F, Hazenberg MD, Tesselaar K, et al. Immune activation and collateral damage in AIDS pathogenesis. Front Immunol. 2013;4:1–14.CrossRefGoogle Scholar
  29. Mohri H, Perelson AS, Tung K, et al. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J Exp Med. 2001;194:1277–87.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Mosier DE, Gulizia RJ, MacIsaac PD, et al. Rapid loss of CD4+ T cells in human-PBL-SCID mice by noncytopathic HIV isolates. Science. 1993;260:689–92.PubMedCrossRefGoogle Scholar
  31. Pakker NG, Notermans DW, de Boer R, et al. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med. 1998;4:208–14.PubMedCrossRefGoogle Scholar
  32. Rey-Cuille MA, Berthier JL, Bomsel-Demontoy MC, et al. Simian immunodeficiency virus replicates to high levels in sooty mangabeys without inducing disease. J Virol. 1998;72:3872–86.PubMedPubMedCentralGoogle Scholar
  33. Roederer M, Dubs JG, Anderson MT, et al. CD8 naive T cell counts decrease progressively in HIV-infected adults. J Clin Invest. 1995;95:2061–6.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Rosenzweig M, Clark DP, Gaulton GN. Selective thymocyte depletion in neonatal HIV-1 thymic infection. AIDS. 1993;7:1601–5.PubMedCrossRefGoogle Scholar
  35. Sandgaard KS, Lewis J, Adams S, et al. Antiretroviral therapy increases thymic output in children with HIV. AIDS. 2014;28:209–14.PubMedCrossRefGoogle Scholar
  36. 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;18:441–52.PubMedCrossRefGoogle Scholar
  37. Teixeira L, Valdez H, McCune JM, et al. Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function. AIDS. 2001;15:1749–56.PubMedCrossRefGoogle Scholar
  38. Tesselaar K, Arens R, van Schijndel GMW, et al. Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions. Nat Immunol. 2003;4:49–54.PubMedCrossRefGoogle Scholar
  39. Vrisekoop N, van Gent R, de Boer AB, et al. Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging. J Immunol. 2008;181:1573–81.PubMedCrossRefGoogle Scholar
  40. Wolthers K, Wisman GBA, Otto SA, et al. T cell telomere length in HIV-1 infection: no evidence for increased CD4+ T cell turnover. Science. 1996;274:1543–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Julia Drylewicz
    • 1
  • Kiki Tesselaar
    • 1
  • José A. M. Borghans
    • 1
  1. 1.Laboratory of Translational Immunology, Department of ImmunologyUniversity Medical Center UtrechtUtrechtThe Netherlands