title: The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin.
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.
authors.affiliation: 1] Department of Microbiology and Immunology, The University of Melbourne, Parkville, Australia. [2].
authors.forename: Laura K
authors.initials: LK
authors.lastname: Mackay
authors.forename: Azad
authors.initials: A
authors.lastname: Rahimpour
authors.forename: Joel Z
authors.initials: JZ
authors.lastname: Ma
authors.forename: Nicholas
authors.initials: N
authors.lastname: Collins
authors.forename: Angus T
authors.initials: AT
authors.lastname: Stock
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Hafon
authors.forename: Javier
authors.initials: J
authors.lastname: Vega-Ramos
authors.forename: Pilar
authors.initials: P
authors.lastname: Lauzurica
authors.forename: Scott N
authors.initials: SN
authors.lastname: Mueller
authors.forename: Tijana
authors.initials: T
authors.lastname: Stefanovic
authors.forename: David C
authors.initials: DC
authors.lastname: Tscharke
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
authors.forename: Thomas
authors.initials: T
authors.lastname: Gebhardt
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D006561:Herpes Simplex / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D039001:Integrin alpha Chains; D019409:Interleukin-15; D037181:Lectins, C-Type; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D011971:Receptors, Immunologic; D018125:Receptors, Transforming Growth Factor beta; D000099192:CD69 Antigens; C451496:Klrg1 protein, mouse; C091367:alpha E integrins