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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / immunology*
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / immunology
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Antigens, Differentiation, T-Lymphocyte / metabolism
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / virology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Flow Cytometry
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Herpes Simplex / immunology
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Herpes Simplex / virology
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Herpesvirus 1, Human / immunology
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Herpesvirus 1, Human / physiology
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Host-Pathogen Interactions / immunology
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Immunologic Memory / immunology*
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Integrin alpha Chains / genetics
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Integrin alpha Chains / immunology*
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Integrin alpha Chains / metabolism
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Interleukin-15 / genetics
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Interleukin-15 / immunology
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Interleukin-15 / metabolism
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Lectins, C-Type / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Mice, Transgenic
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Oligonucleotide Array Sequence Analysis
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / immunology
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Protein Serine-Threonine Kinases / metabolism
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / immunology
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Receptors, Transforming Growth Factor beta / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Skin / immunology*
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Skin / metabolism
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Skin / virology
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Transcriptome / genetics
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Transcriptome / immunology
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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Integrin alpha Chains
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Interleukin-15
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Klrg1 protein, mouse
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Lectins, C-Type
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Receptors, Immunologic
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Receptors, Transforming Growth Factor beta
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alpha E integrins
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II