Encyclopedia of AIDS

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

Role of Regulatory T Cells During HIV Infection

  • Claire A. Chougnet
  • Maria E. Moreno-Fernandez
  • Cesar M. Rueda
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9610-6_202-1


Human immunodeficiency virus (HIV) causes a gradual loss of immune competence, leading to acquired immunodeficiency syndrome (AIDS). HIV-associated defects in cell-mediated immunity (CMI) are of particular importance, as these impairments lead to poor control of HIV replication and of other pathogens whose clearance depends on CMI. Importantly, a number of immune deficits caused by HIV infection can be partially restored in vitro, suggesting the existence of active regulatory mechanisms. Several mechanisms are involved in the regulation of the immune system; among these is the pivotal role of regulatory T cells (Treg), a subset of CD4+T cells, which has been recognized for several years. In addition to their role in controlling peripheral tolerance, Treg promote the establishment of persistent infections (viral, bacterial, parasitic, and fungal). Treg may thus contribute to inefficient CMI during chronic HIV infection. However, Treg may also play a beneficial role, because...


Human Immunodeficiency Virus Human Immunodeficiency Virus Infection Rhesus Macaque Human Immunodeficiency Virus Patient Human Immunodeficiency Virus Replication 
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  1. Allers K. 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. 2010;84(7):3259–69.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Amarnath S. Endogenous TGF-beta activation by reactive oxygen species is key to Foxp3 induction in TCR-stimulated and HIV-1-infected human CD4+CD25- T cells. Retrovirology. 2007;4:57.PubMedCrossRefPubMedCentralGoogle Scholar
  3. Boasso A. Regulatory T-cell markers, indoleamine 2,3-dioxygenase, and virus levels in spleen and gut during progressive simian immunodeficiency virus infection. J Virol. 2007;81(21):11593–603.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Chase AJ. Preservation of FoxP3+ regulatory T cells in the peripheral blood of human immunodeficiency virus type 1-infected elite suppressors correlates with low CD4+ T-cell activation. J Virol. 2008;82(17):8307–15.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Elahi S. Protective HIV-specific CD8+ T cells evade Treg cell suppression. Nat Med. 2011;17(8):989–95.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Estes JD. 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. 2007;195(4):551–61.PubMedCrossRefGoogle Scholar
  7. Genesca M. Live-attenuated lentivirus immunization modulates innate immunity and inflammation while protecting rhesus macaques from vaginal simian immunodeficiency virus challenge. J Virol. 2012;86(17):9188–200.PubMedCrossRefPubMedCentralGoogle Scholar
  8. Hryniewicz A. CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques. Blood. 2006;108(12):3834–42.PubMedCrossRefPubMedCentralGoogle Scholar
  9. Ji J. HIV-1 binding to CD4 on CD4+CD25+ regulatory T cells enhances their suppressive function and induces them to home to, and accumulate in, peripheral and mucosal lymphoid tissues: an additional mechanism of immunosuppression. Int Immunol. 2009;21(3):283–94.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Kared H. HIV-specific regulatory T cells are associated with higher CD4 cell counts in primary infection. AIDS. 2008;22(18):2451–60.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Kinter AL. CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status. J Exp Med. 2004;200(3):331–43.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Kornfeld C. Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. J Clin Invest. 2005;115(4):1082–91.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Legrand FA. Strong HIV-1-specific T cell responses in HIV-1-exposed uninfected infants and neonates revealed after regulatory T cell removal. PLoS One. 2006;1:e102.PubMedCrossRefPubMedCentralGoogle Scholar
  14. Lim AY. Cell surface markers of regulatory T cells are not associated with increased forkhead box p3 expression in blood CD4+ T cells from HIV-infected patients responding to antiretroviral therapy. Immunol Cell Biol. 2006;84(6):530–6.PubMedCrossRefGoogle Scholar
  15. Liu J. Neuromodulatory activities of CD4+CD25+ regulatory T cells in a murine model of HIV-1-associated neurodegeneration. J Immunol. 2009;182(6):3855–65.PubMedCrossRefPubMedCentralGoogle Scholar
  16. Manches O. HIV-activated human plasmacytoid DCs induce Tregs through an indoleamine 2,3-dioxygenase-dependent mechanism. J Clin Invest. 2008;118(10):3431–9.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Moreno-Fernandez ME. 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. 2009;83(24):12925–33.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Moreno-Fernandez ME. Regulatory T, cells control HIV replication in activated T cells through a cAMP-dependent mechanism. Blood. 2011;117(20):5372–80.PubMedCrossRefPubMedCentralGoogle Scholar
  19. Moreno-Fernandez ME. Regulatory T cells diminish HIV infection in dendritic cells – conventional CD4(+) T cell clusters. Front Immunol. 2014;5:199.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Ndhlovu LC. FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection. J Leukoc Biol. 2008;83(2):254–62.PubMedCrossRefGoogle Scholar
  21. Nikolova M. CD39/adenosine pathway is involved in AIDS progression. PLoS Pathog. 2011;7(7):e1002110.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Nilsson J. HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood. 2006;108(12):3808–17.PubMedCrossRefPubMedCentralGoogle Scholar
  23. Presicce P. Frequency of circulating regulatory T cells increases during chronic HIV infection and is largely controlled by highly active antiretroviral therapy. PLoS One. 2011;6(12):e28118.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Presicce P. Myeloid dendritic cells isolated from tissues of SIV-infected Rhesus macaques promote the induction of regulatory T cells. AIDS. 2012;26(3):263–73.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Rueda CM. Incomplete normalization of regulatory t-cell frequency in the gut mucosa of Colombian HIV-infected patients receiving long-term antiretroviral treatment. PLoS One. 2013;8(8):e71062.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Claire A. Chougnet
    • 1
  • Maria E. Moreno-Fernandez
    • 1
  • Cesar M. Rueda
    • 1
  1. 1.Department of ImmunobiologyCincinnati Children Hospital Medical CenterCincinnatiUSA