Research ArticleT CELLS

IL-21 from high-affinity CD4 T cells drives differentiation of brain-resident CD8 T cells during persistent viral infection

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Science Immunology  18 Sep 2020:
Vol. 5, Issue 51, eabb5590
DOI: 10.1126/sciimmunol.abb5590

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CD4 T cells are critical for the development of tissue-resident memory (TRM) CD8 T cells during persistent viral infection of the central nervous system with polyomavirus. Ren et al. identified a role for IL-21 produced by virus-specific high-affinity CD4 T cells in driving differentiation of brain CD8 T cells into TRM. IL21R−/− brain CD8 T cells have defects in antigen recall and oxidative metabolism and fail to differentiate into TRM. CD4 T cell–deficient mice had similar defects in gene expression related to TRM development, but intrathecal delivery of IL-21 reversed these deficiencies. These results provide critical insight into the role of IL-21 production by high-affinity CD4 T cells in driving differentiation of brain TRM during persistent viral infection.

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