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

Abstract

Much remains unknown about the roles of CD4⁺ T helper cells in shaping localized memory B cell and CD8⁺ T cell immunity in the mucosal tissues. Here, we report that lung T helper cells provide local assistance for the optimal development of tissue-resident memory B and CD8⁺ T cells after the resolution of primary influenza virus infection. We have identified a population of T cells in the lung that exhibit characteristics of both follicular T helper and T_RM cells, and we have termed these cells as resident helper T (T_RH) cells. Optimal T_RH cell formation was dependent on transcription factors involved in T follicular helper and resident memory T cell development including BCL6 and Bhlhe40. We show that T_RH cells deliver local help to CD8⁺ T cells through IL-21-dependent mechanisms. Our data have uncovered the presence of a tissue-resident helper T cell population in the lung that plays a critical role in promoting the development of protective B cell and CD8⁺ T cell responses.