Journal
SCIENCE
Volume 366, Issue 6462, Pages 202-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aav5728
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Funding
- Bob and Laura Reynolds MGH Research Scholar Award
- NIH [R21 AR070981, R01 AI040618, T32 CA207201, T32 AR007258, R01 AI121546, R01 AI107087]
- Wellcome Trust [203128/Z/16/Z]
- BBSRC [BB/R003114/1] Funding Source: UKRI
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Epithelial resident memory T (eT(RM)) cells serve as sentinels in barrier tissues to guard against previously encountered pathogens. How eT(RM) 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 beta (TGF-beta) epigenetically conditions resting naive CD8(+) T cells and prepares them for the formation of eT(RM) cells in a mouse model of skin vaccination. Naive 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-beta-activating alpha(V) integrins. Thus, the preimmune T cell repertoire is actively conditioned for a specialized memory differentiation fate through signals restricted to LNs.
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