IL-27 Induces IFM/STAT1-Dependent Genes and Enhances Function of TIGIT+ HIVgag-Specific T Cells

Abstract

HIV-specific T cells have diminished effector function and fail to control/eliminate the virus. IL-27, a member of the IL-6/IL-12 cytokine superfamily has been shown to inhibit HIV replication. However, whether or not IL-27 can enhance HIV-specific T cell function is largely unknown. In this study, we investigated the role of IL-27 signaling in human T cells by evaluating the global transcriptional changes and its impact in the function of HIV-specific T cells. We found that T cells from people living with HIV (PLWH), expressed higher levels of STAT1 leading to enhanced STAT1 activation upon IL-27 stimulation than healthy controls. Observed IL-27 induced transcriptional changes were associated with IFN/STAT1-dependent pathways in CD4 and CD8 T cells. In addition, IL-27 enhanced perforin and CD107a production suggest its potential role in T cell cytotoxicity. Importantly, IL-27 dependent modulation of T-bet expression promoted IFN-gamma secretion by TIGIT+HIVGag-specific T cells. Moreover, we showed the anti-HIV property of IL-27 in cells isolated from HIV-suppressed PLWH with in vitro HIV reactivation. This new immunomodulatory effect of IL-27 on HIV-specific T cell function and its anti-HIV properties suggest the potential therapeutic use of IL-27 in cure strategies.