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

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Science Immunology  08 Jan 2021:
Vol. 6, Issue 55, eabb6852
DOI: 10.1126/sciimmunol.abb6852

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Resident help for fighting influenza

Memory T cells take up residence in the lung after respiratory virus infection to facilitate rapid and localized immune responses during reinfection. Two studies in this week’s issue identify a population of CD4+ tissue–resident helper T cells in mice that are BCL6-dependent and support antiviral B cell responses within inducible bronchus-associated lymphoid tissue after influenza infection. Swarnalekha et al. used single-cell RNA sequencing of antigen-specific T cells across different tissues to characterize lung T resident helper cells and demonstrated that their development also requires B cells. Son et al. showed that T resident helper cells rely on Bhlhe40 for their survival and support protective CD8+ T cell responses by producing IL-21. These studies provide insight into the function of mucosal tissue-resident CD4+ T cells during viral infection. See related Research Article by Swarnalekha et al. and Focus by Schattgen et al. in this issue.


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 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.

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