CD4+ and CD8+ T cells expressing FoxP3 in HIV-infected patients are phenotypically distinct and influenced by disease severity and antiretroviral therapy
- PMID: 19363449
- DOI: 10.1097/QAI.0b013e3181a74fad
CD4+ and CD8+ T cells expressing FoxP3 in HIV-infected patients are phenotypically distinct and influenced by disease severity and antiretroviral therapy
Abstract
Objectives: Forkhead box P3 (FoxP3) is critical for the development of CD4 regulatory T (Treg) cells and is a useful marker to identify this population. Recently, expression of FoxP3 was reported in human CD8 T cells from the blood of untreated HIV-infected individuals. We assessed whether FoxP3 expression in CD8 T cells is associated with suppressive potential and/or with HIV-associated immune activation.
Methods: FoxP3CD8 T cells in non-HIV donors and in untreated and treated HIV-infected patients were identified by flow cytometry, then examined for coexpression of other Treg cell-associated markers [cytotoxic T lymphocyte-associated antigen (CTLA)-4, GITR, and CD45RO], markers of activation [HLA-DR, Ki-67, and programmed death (PD)-1], and markers of senescence (CD57 without CD28).
Results: Similar proportions of FoxP3-expressing CD4 and CD8 T cells coexpressed HLA-DR and Ki-67. However, compared with FoxP3CD4 cells, FoxP3CD8 cells expressed less CTLA-4, CD28, and CD45RO but more PD-1 and CD57. FoxP3-expressing CD4 and CD8 cells from untreated patients exhibited higher expression of HLA-DR, Ki-67, and PD-1 compared with non-HIV donors and treated patients.
Conclusions: FoxP3CD8 T cells are phenotypically distinct from FoxP3CD4 and FoxP3CD8 T cells. Expression of FoxP3 is associated with cellular activation in both CD4 and CD8 T cells.
Similar articles
-
FOXP3+Helios+ Regulatory T Cells, Immune Activation, and Advancing Disease in HIV-Infected Children.J Acquir Immune Defic Syndr. 2016 Aug 15;72(5):474-84. doi: 10.1097/QAI.0000000000001000. J Acquir Immune Defic Syndr. 2016. PMID: 27003495 Free PMC article.
-
Severe immune dysregulation affects CD4⁺CD25(hi)FoxP3⁺ regulatory T cells in HIV-infected patients with low-level CD4 T-cell repopulation despite suppressive highly active antiretroviral therapy.J Infect Dis. 2012 May 15;205(10):1501-9. doi: 10.1093/infdis/jis230. Epub 2012 Mar 28. J Infect Dis. 2012. PMID: 22457273
-
HIV-induced T-cell activation/exhaustion in rectal mucosa is controlled only partially by antiretroviral treatment.PLoS One. 2012;7(1):e30307. doi: 10.1371/journal.pone.0030307. Epub 2012 Jan 19. PLoS One. 2012. PMID: 22276176 Free PMC article.
-
CD8+ CD28- and CD8+ CD57+ T cells and their role in health and disease.Immunology. 2011 Sep;134(1):17-32. doi: 10.1111/j.1365-2567.2011.03470.x. Epub 2011 Jun 29. Immunology. 2011. PMID: 21711350 Free PMC article. Review.
-
The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology.Immunol Rev. 2006 Aug;212:131-48. doi: 10.1111/j.0105-2896.2006.00419.x. Immunol Rev. 2006. PMID: 16903911 Review.
Cited by
-
Early short-term antiretroviral therapy is associated with a reduced prevalence of CD8(+)FoxP3(+) T cells in simian immunodeficiency virus-infected controller rhesus macaques.AIDS Res Hum Retroviruses. 2011 Jul;27(7):763-75. doi: 10.1089/AID.2010.0251. Epub 2011 Jan 17. AIDS Res Hum Retroviruses. 2011. PMID: 21142402 Free PMC article.
-
Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection.Front Immunol. 2022 Jul 28;13:947647. doi: 10.3389/fimmu.2022.947647. eCollection 2022. Front Immunol. 2022. PMID: 35967422 Free PMC article.
-
HIV-1 shedding from the female genital tract is associated with increased Th1 cytokines/chemokines that maintain tissue homeostasis and proportions of CD8+FOXP3+ T cells.J Acquir Immune Defic Syndr. 2014 Dec 1;67(4):357-64. doi: 10.1097/QAI.0000000000000336. J Acquir Immune Defic Syndr. 2014. PMID: 25202922 Free PMC article.
-
The Complex Role of Regulatory T Cells in Immunity and Aging.Front Immunol. 2021 Jan 27;11:616949. doi: 10.3389/fimmu.2020.616949. eCollection 2020. Front Immunol. 2021. PMID: 33584708 Free PMC article. Review.
-
Homeostasis and function of regulatory T cells in HIV/SIV infection.J Virol. 2012 Oct;86(19):10262-9. doi: 10.1128/JVI.00993-12. Epub 2012 Jul 18. J Virol. 2012. PMID: 22811537 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials