The role of cytokines which signal through the common gamma chain cytokine receptor in the reversal of HIV specific CD4(+) and CD8(+) T cell anergy

PLoS One. 2007 Mar 21;2(3):e300. doi: 10.1371/journal.pone.0000300.

Abstract

Background: HIV specific T cells are putatively anergic in vivo. IL-2, a member of a class of cytokines that binds to receptors containing the common gamma chain (gammac) has been shown to reverse anergy. We examined the role of gammac cytokines in reversing HIV specific T cell anergy.

Methods: PBMC from untreated HIV-infected individuals were briefly exposed to a panel of gammac cytokines, and frequencies of gag specific T cells were enumerated by intracellular IFN-gamma flow cytometry.

Results: Of the gammac cytokines, brief exposure to IL-2, IL-15, or combined IL-15/IL-7 significantly enhanced (range 2-7 fold) the CD4(+) and CD8(+) T cell IFN-gamma responses to HIV gag, with IL-15 giving the greatest enhancement. The effects of cytokines were not due to enhanced proliferation of pre-existing antigen specific cells, but were due to a combination of enhanced cytokine production from antigen specific T cells plus activation of non-epitope specific T cells.

Conclusions: These observations support the notion that a significant number of HIV specific T cells are circulating in an anergic state. IL-2, IL-7 and particularly IL-15 as an immune modulator to reverse HIV-1 specific T cell anergy should be investigated, with the caveat that non-specific activation of T cells may also be induced.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Division
  • Chronic Disease
  • Clonal Anergy
  • Cytokines / immunology
  • Cytokines / physiology
  • Disease Progression
  • HIV Infections / immunology*
  • HIV Infections / physiopathology
  • HIV-1 / immunology*
  • Humans
  • Interleukin Receptor Common gamma Subunit / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Cytokines
  • Interleukin Receptor Common gamma Subunit