The Developmental Pathway for CD103(+)CD8+ Tissue-Resident Memory T Cells of Skin

Nat Immunol. 2013 Dec;14(12):1294-301. doi: 10.1038/ni.2744. Epub 2013 Oct 27.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Flow Cytometry
  • Herpes Simplex / immunology
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / immunology
  • Herpesvirus 1, Human / physiology
  • Host-Pathogen Interactions / immunology
  • Immunologic Memory / immunology*
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / immunology*
  • Integrin alpha Chains / metabolism
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology
  • Interleukin-15 / metabolism
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / immunology
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / immunology
  • Receptors, Transforming Growth Factor beta / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Skin / immunology*
  • Skin / metabolism
  • Skin / virology
  • Transcriptome / genetics
  • Transcriptome / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Integrin alpha Chains
  • Interleukin-15
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, Immunologic
  • Receptors, Transforming Growth Factor beta
  • alpha E integrins
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II

Associated data

  • GEO/GSE47045