The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin
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Authors
Mackay, Laura K
Rahimpour, Azad
Ma, Joel Z
Collins, Nicholas
Stock, Angus T
Hafon, Ming-Li
Vega-Ramos, Javier
Lauzurica, Pilar
Mueller, Scott N
Stefanovic, Tijana
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Nature Publishing Group
Abstract
Tissue-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.
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Keywords
Animals, Antigens, CD, Antigens, Differentiation, T-Lymphocyte, CD8-Positive T-Lymphocytes, Cell Differentiation, Flow Cytometry, Herpes Simplex, Herpesvirus 1, Human, Host-Pathogen Interactions, Immunologic Memory, Integrin alpha Chains, Interleukin-15, Lectins, C-Type, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Knockout, Mice, Transgenic, Oligonucleotide Array Sequence Analysis, Protein-Serine-Threonine Kinases, Receptors, Immunologic, Receptors, Transforming Growth Factor beta, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Skin, Transcriptome
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Nature immunology