Nature Research, Nature Immunology, 12(14), p. 1294-1301, 2013
DOI: 10.1038/ni.2744
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Tissue-resident memory T cells (TRM cells) provide superior protection against infection in extralymphoid tissues. Here we found that CD103(+)CD8(+) TRM cells developed in the skin from epithelium-infiltrating precursor cells that lacked expression of the effector-cell marker KLRG1. A combination of entry into the epithelium plus local signaling by interleukin 15 (IL-15) and transforming growth factor-β (TGF-β) was required for the formation of these long-lived memory cells. Notably, differentiation into TRM cells resulted in the progressive acquisition of a unique transcriptional profile that differed from that of circulating memory cells and other types of T cells that permanently reside in skin epithelium. We provide a comprehensive molecular framework for the local differentiation of a distinct peripheral population of memory cells that forms a first-line immunological defense system in barrier tissues.