Mackay, Laura KRahimpour, AzadMa, Joel ZCollins, NicholasStock, Angus THafon, Ming-LiVega-Ramos, JavierLauzurica, PilarMueller, Scott NStefanovic, TijanaTscharke, David CHeath, William RInouye, MichaelCarbone, Francis RGebhardt, Thomas2015-03-122015-03-121529-2908http://hdl.handle.net/1885/12900Tissue-resident memory T cells (T(RM) cells) provide superior protection against infection in extralymphoid tissues. Here we found that CD103(+)CD8(+) T(RM) 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 T(RM) 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.Supported by National Health and Medical Research Council of Australia and Australian Research Council.http://www.sherpa.ac.uk/romeo/issn/1529-2908/..."Authors retain copyright, Author's pre-print on arXiv or bioRXiv, Author's post-print on author's personal website, institutional repository, PubMed Central or funding body's archive, Published source must be acknowledged, Must link to publisher version with DOI, Publisher's version/PDF cannot be used" from SHERPA/RoMEO site (as at 23/03/15)AnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteCD8-Positive T-LymphocytesCell DifferentiationFlow CytometryHerpes SimplexHerpesvirus 1, HumanHost-Pathogen InteractionsImmunologic MemoryIntegrin alpha ChainsInterleukin-15Lectins, C-TypeMiceMice, Inbred C57BLMice, Inbred StrainsMice, KnockoutMice, TransgenicOligonucleotide Array Sequence AnalysisProtein-Serine-Threonine KinasesReceptors, ImmunologicReceptors, Transforming Growth Factor betaReverse Transcriptase Polymerase Chain ReactionSignal TransductionSkinTranscriptome2013-10-1010.1038/ni.27442015-12-11