Lower STAT1 expression by Type I IFN receptor-deficient CD4 T cells responding against Influenza virus cannot account for reduced Th1 hallmarks compared to wildtype CD4 T cells 3138

Abstract Description Delineating how distinct cytokine signals impact the efficacy of CD4 T cell responses against Influenza A virus (IAV) is an important goal. We showed that IAV-primed STAT1-/- but not STAT4-/- CD4 T cells have reduced Th1 identity versus WT CD4 T cells. As type I interferons (IFN-I) can signal through STAT1 and STAT4, we investigated here how direct IFN-I signals impact anti-IAV CD4 T cell responses. We first compared IAV-specific WT and IFN-I receptor-deficient (IFNAR-/-) CD4 T cells in infected WT mice. Th1 hallmarks were reduced in IFNAR-/- cells, which correlated with reduced STAT1 but not STAT4 expression compared to WT cells. Furthermore, IFN-I signaling upregulated STAT1 but not STAT4 levels in WT CD4 T cells activated in vitro. To determine if STAT1 expression levels affect anti-viral CD4 T cell responses, we generated STAT1+/- CD4 T cells, which express less STAT1 than WT cells when activated in vitro, mirroring patterns seen comparing WT and IFNAR-/- effector cells. We transferred equal numbers of virus-specific WT and STAT1+/- cells to WT hosts and compared the donor cells at the peak of the T cell response after IAV infection. The Th1 identity of STAT1+/- cells mirrored that of WT CD4 T cells. This indicates that lower STAT1 expression alone cannot account for the weaker Th1 imprint of IAV-primed IFNAR-/- CD4 T cells. Our data offers insight for further studies exploring how IFN-I can be leveraged to enhance vaccine-induced antiviral T-cell immunity. Funding Sources NIH R01 grant -1R01AI167994-01 Topic Categories Viral Immunology (VIR)