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 Sep;82(17):8307-15. doi: 10.1128/JVI.00520-08. Epub 2008 Jun 25.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology
  • Case-Control Studies
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / analysis
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • HIV Infections / blood*
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Lymphocyte Activation
  • Male
  • T-Lymphocytes, Regulatory / immunology
  • Viral Load
  • Viremia

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors