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.
Elite suppressors (ES) are untreated human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain normal CD4(+) T-cell counts and control viremia to levels that are below the limit of detection of current assays. The mechanisms involved in long-term control of viremia have not been fully elucidated. CD4(+) CD25(+) regulatory T cells (Tregs) downmodulate chronic inflammation by suppressing the activation and proliferation of effector lymphocytes. We found that while Tregs were functional in ES and patients on highly active antiretroviral therapy (HAART), ES maintained high levels of Tregs in peripheral blood mononuclear cells whereas patients on HAART had evidence of Treg depletion. We also demonstrated that Tregs can serve as reservoirs for HIV-1 in vivo. These data suggest that both direct infection by HIV-1 and tissue redistribution are possible explanations for declining FoxP3(+) Tregs in progressive HIV-1 infection. Furthermore, the maintenance of Tregs may be one mechanism associated with the nonprogressive nature of HIV-1 infection in ES.
Chase
Amanda J
AJ
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yang
Hung-Chih
HC
Zhang
Hao
H
Blankson
Joel N
JN
Siliciano
Robert F
RF
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000097:blood* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019562:Viral Load; D014766:Viremia
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors