Migratory DCs activate TGF-β to precondition naïve CD8+ T cells for tissue-resident memory fate

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Abstract

Epithelial resident memory T (eTRM) cells serve as sentinels in barrier tissues to guard against previously encountered pathogens. How eTRM cells are generated has important implications for efforts to elicit their formation through vaccination or prevent it in autoimmune disease. Here, we show that during immune homeostasis, the cytokine transforming growth factor β (TGF-β) epigenetically conditions resting naïve CD8+ T cells and prepares them for the formation of eTRM cells in a mouse model of skin vaccination. Naïve T cell conditioning occurs in lymph nodes (LNs), but not in the spleen, through major histocompatibility complex class I–dependent interactions with peripheral tissue–derived migratory dendritic cells (DCs) and depends on DC expression of TGF-β–activating αV integrins. Thus, the preimmune T cell repertoire is actively conditioned for a specialized memory differentiation fate through signals restricted to LNs.

Bibliographical metadata

Original languageEnglish
JournalScience
Volume366
Issue number6462
DOIs
Publication statusPublished - 11 Oct 2019