Loss of CD4 T cell responses to prior vaccines associate with inflammation and altered transcriptional signatures in HIV infection

The preference of HIV to infect activated CD4 T cells has been proposed to contribute to a numerical reduction of antigen-specific T cells and the loss of T cell-mediated immunity. To date, our understanding of how HIV impact on vaccine-induced cellular immunity is limited. Moreover, the influence of chronic inflammation, that persist in treated HIV infection, is still unclear. Here, we investigated inflammation, immune activation and antigen-specific T cell responses in HIV-uninfected and cART-treated HIV people with prior measles virus and tetanus toxoid immunity. Our findings highlight lower antigen-induced T cell activation and lower cytokine production of antigen-specific CD4 T cells in the HIV group. These lower recall CD4 T cell responses associated with high plasma levels of multiple cytokines and with T cell hyperactivation. Transcriptome analysis of sorted antigen-specific CD4 T cells revealed that upon antigen reencounter, HIV people on cART had a reduced expression of gene sets previously reported to associate with vaccine-induced protective immunity against various pathogens. We further identified a consistent impairment of the IFN? and IFN? signaling pathways as a mechanism for the functional loss of antigen-specific CD4 T cell responses in cART-treated people with HIV. Together, our findings suggest that vaccine-induced cellular immunity may benefit from strategies to counteract inflammation in HIV infection.pecific Overall design: T cell subsets sorted after stimulation with MV, TT or a no stim control underwent RNA extraction, followed by NEB next library prep and illuminy sequencing