Tissue-resident CD4⁺ T helper cells assist protective respiratory mucosal B and CD8⁺ T cell memory responses

Abstract

The roles of CD4⁺ T helper cells (T_H) in shaping localized memory B and CD8⁺ T cell immunity in the mucosal tissues are largely unexplored. Here, we report that lung T_H cells provide local assistance for the optimal development of tissue-resident memory B (B_RM) and CD8⁺ T (T_RM) cells following the resolution of primary influenza virus infection. We identify a population of tissue-resident CD4⁺ T_H (aka T_RH) cells that co-exhibit follicular T helper (T_FH) and T_RM cell features and mediate local help of CD4⁺ T cells to B and CD8⁺ T cells. Optimal T_RH cell formation requires lung B cells and transcription factors involved in T_FH or T_RM development. Further, we show that T_RH cells deliver local help to B and CD8 T cells through CD40L and IL-21-dependent mechanisms. Our data have uncovered a new tissue-resident T_H cell population that is specialized in assisting the development of mucosal protective B and CD8⁺ T cell responses in situ.