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

Son, Y. M.; Cheon, I. S.; Wu, Y.; Li, C.; Wang, Z.; Chen, Y.; Takahashi, Y.; Dent, A.; Kaplan, M.; Fu, Y.-X.; Taylor, J.; Cui, W.; Sun, J.

doi:10.1101/2020.02.28.970400

bioRxiv · 10.1101/2020.02.28.970400

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

Son, Y. M.·Cheon, I. S.·Wu, Y.·Li, C.·Wang, Z.·Chen, Y.·Takahashi, Y.·Dent, A.·Kaplan, M.·Fu, Y.-X.·Taylor, J.·Cui, W.·Sun, J.

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Abstract

The roles of CD4+ T helper cells (TH) in shaping localized memory B and CD8+ T cell immunity in the mucosal tissues are largely unexplored. Here, we report that lung TH cells provide local assistance for the optimal development of tissue-resident memory B (BRM) and CD8+ T (TRM) cells following the resolution of primary influenza virus infection. We identify a population of tissue-resident CD4+ TH (aka TRH) cells that co-exhibit follicular T helper (TFH) and TRM cell features and mediate local help of CD4+ T cells to B and CD8+ T cells. Optimal TRH cell formation requires lung B cells and transcription factors involved in TFH or TRM development. Further, we show that TRH 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 TH cell population that is specialized in assisting the development of mucosal protective B and CD8+ T cell responses in situ.

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Son, Y. M., Cheon, I. S., Wu, Y., Li, C., Wang, Z., Chen, Y., Takahashi, Y., Dent, A., Kaplan, M., Fu, Y.-X., Taylor, J., Cui, W., Sun, J.. 2020-02-28. Tissue-resident CD4+ T helper cells assist protective respiratory mucosal B and CD8+ T cell memory responses. https://doi.org/10.1101/2020.02.28.970400

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