Son, Young MinCheon, In SuWu, YueLi, ChaofanWang, ZhengGao, XiaochenChen, YaoTakahashi, YoshimasaFu, Yang-XinDent, Alexander L.Kaplan, Mark H.Taylor, Justin J.Cui, WeiguoSun, Jie2024-08-152024-08-152021Son YM, Cheon IS, Wu Y, et al. Tissue-resident CD4+ T helper cells assist the development of protective respiratory B and CD8+ T cell memory responses. Sci Immunol. 2021;6(55):eabb6852. doi:10.1126/sciimmunol.abb6852https://hdl.handle.net/1805/42809Much 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.en-USPublisher PolicyBasic helix-loop-helix transcription factorsHomeodomain proteinsHuman influenzaLungRespiratory mucosaArticle