TCF-1 dictates lung tissue resident helper T cell and memory B cell development during flu

Abstract Influenza (flu) infections are a significant cause of annual human morbidity and mortality. The efficacy seasonal flu vaccines depends on the accuracy prediction circulating strains for upcoming season. To develop that broadly effective more sustainable, induction cross-reactive memory immunity is desirable. Flu infection induces tissue resident T (Trm) B (Brm) cells which rapidly respond to reinfection. Tissue helper (Trh) population follicular (Tfh)-like CD4 +Trm promote development Brm cell responses following infection. transcription factor TCF-1, encoded by Tcf7, critical in both Tfh viral infections. However, role TCF-1 Trh has not been investigated. Utilizing Tcf7 fl/flCD4 Creconditional knockout mouse model conjunction with intravascular labeling influenza A peptide MHC Class II tetramers, we found required differentiation flu-specific cells, as well optimal Most significantly, upon heterosubtypic reinfection, fl/flcontrol mice expanded while it became undetectable Cremice, coinciding severely impaired lung germinal center CD138 +plasma response. Together, our data indicates response This work implications universal vaccines.