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.
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.
Gu
Xiao Xiao Jenny
XX
Clinical Sciences Division, University of Toronto, Toronto, Canada.
Yue
Feng Yun
FY
Kovacs
Colin M
CM
Ostrowski
Mario A
MA
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002908:Chronic Disease; D017635:Clonal Anergy; D016207:Cytokines / Q000276:immunology / Q000502:physiology; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D053631:Interleukin Receptor Common gamma Subunit