Type I interferon increases the sensitivity of human immunodeficiency virus (HIV)-specific CD8+ T lymphocytes to CD95/Fas-mediated apoptosis (42.22)

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Abstract Innate immune responses elicited during acute and chronic HIV infection are critical to the control of viremia. Based on their well established antiviral effects, the production of type I interferon (IFN-alpha and IFN-beta) has long been considered a protective mechanism in HIV infection. However, it is possible that excessive IFN-alpha and IFN-beta production during HIV infection may impair HIV-specific CD8+ T cell responses and/or contribute to the loss of CD4+ T cells. We show here that CD4+ and CD8+ T lymphocytes from healthy donors and HIV+ patients are sensitized to CD95/Fas-induced death when pre-incubated with type I interferon for 72 hours. Importantly, IFN-alpha increased the sensitivity of HIV-specific CD8+ T cells from HIV+ individuals to CD95/Fas-mediated apoptosis. Apoptosis of CMV-specific and EBV-specific CD8+ T cells from the same patients was not augmented when exposed to IFN-alpha and subsequently stimulated with anti-CD95 antibody. Since CD4+ T cells and HIV-specific CD8+ T cells in HIV infection are known to be sensitive to CD95/Fas-mediated apoptosis, our studies suggest that these lymphocytes may be initially sensitized to CD95/Fas-induced death by type 1 interferon during acute HIV infection. The production of these anti-viral cytokines during chronic infection may further compromise CD4+ and HIV-specific CD8+ T cell survival.