IRF3 deficiency contributes to impaired memory T cell function in response to influenza infection (IRM14P.453)

Abstract

Abstract The role of IRF3 in initiating the type I interferon response in innate immune cells has been well studied in the context of viral infection. However, it remains unclear what impact IRF3 has in shaping and maintaining adaptive immune responses. To address this, IRF3 deficient (IRF3 KO) mice were infected with influenza A virus (IAV) and T cell responses measured. At day 9 post infection, the frequency of IFN-γ and Granzyme B (GrB) positive T cells were similar between IRF3 KO and wildtype mice. Despite similar primary responses, IRF3 KO mice exhibited significant deficits in recall memory T cell responses to IAV with reduced expression of IFN-γ and GrB. Since IRF3 has been implicated in the expression of cytokines that influence effector and memory T cells responses, cytokine supplementation studies were performed. Addition of IL-12 was the only cytokine tested that was able to rescue the IFN-γ deficiencies in IRF3 KO T cells. Interestingly, peptide specific GrB re-expression could not be restored by any cytokines tested. These results suggest that IRF3 plays a role in the maintenance of antigen specific memory T cell responses and that IRF3 deficiency has a substantial impact on the cytotoxic potential of memory T cells and recall responses. Together, this work provides further insight into the molecular regulation of adaptive immune responses to viral infections and may serve to inform future vaccine strategies that require the development of memory T cells.