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Item Tissue-resident CD4+ T helper cells assist the development of protective respiratory B and CD8+ T cell memory responses(American Association for the Advancement of Science, 2021) Son, Young Min; Cheon, In Su; Wu, Yue; Li, Chaofan; Wang, Zheng; Gao, Xiaochen; Chen, Yao; Takahashi, Yoshimasa; Fu, Yang-Xin; Dent, Alexander L.; Kaplan, Mark H.; Taylor, Justin J.; Cui, Weiguo; Sun, Jie; Microbiology and Immunology, School of MedicineMuch 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 TRM cells, and we have termed these cells as resident helper T (TRH) cells. Optimal TRH 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 TRH 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.