The common γ c subunit molecule is shared among all γ c cytokines and clearly involved in T-cell function, but its role in HIV infection and immunity is not well understood. Here, we examined expression and function of γ c on T cells during SIV infection in Rhesus macaques. Surface γ c distribution was differentially expressed on CD4 + and CD8 + T cells, and CD4 + naive/memory cell populations in various lymphoid tissues of normal macaques. However, surface γ c expression was rapidly and significantly down-regulated on T cells in acute infection with pathogenic SIV, compared to infection with a less virulent SHIV or controls and did not recover on CD8 + T cells in the chronic stage. Moreover, the peripheral and CD4 +T cell loss was inversely correlated with γ c +CD8 + T cells in individual tissues. γ c + T cells were mainly functional as evidenced by higher cytokine secretion and proliferative capacity. Further in vitro experiments found that surface γ c expression could be down-regulated following high level of IL-7 treatment by both internalization and shedding. Down-regulation of γ c during early HIV/SIV infection may inhibit T-cell function, particularly of CD8 + T cells, and, may be linked with immune failure and loss of viral containment.
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