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.

Autor: Xiao Xiao Jenny Gu, Feng Yun Yue, Colin M Kovacs, Mario A Ostrowski
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Zdroj: PLoS ONE, Vol 2, Iss 3, p e300 (2007)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0000300
Popis: 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.
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