title: Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells.
abstract: The skin of an adult human contains about 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice, but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in human skin. We discriminated resident from recirculating T cells in human-engrafted mice and lymphoma patients using alemtuzumab, a medication that depletes recirculating T cells from skin, and then analyzed these T cell populations in healthy human skin. All nonrecirculating resident memory T cells (TRM) expressed CD69, but most were CD4(+), CD103(-), and located in the dermis, in contrast to studies in mice. Both CD4(+) and CD8(+) CD103(+) TRM were enriched in the epidermis, had potent effector functions, and had a limited proliferative capacity compared to CD103(-) TRM. TRM of both types had more potent effector functions than recirculating T cells. We observed two distinct populations of recirculating T cells, CCR7(+)/L-selectin(+) central memory T cells (TCM) and CCR7(+)/L-selectin(-) T cells, which we term migratory memory T cells (TMM). Circulating skin-tropic TMM were intermediate in cytokine production between TCM and effector memory T cells. In patients with cutaneous T cell lymphoma, malignant TCM and TMM induced distinct inflammatory skin lesions, and TMM were depleted more slowly from skin after alemtuzumab, suggesting that TMM may recirculate more slowly. In summary, human skin is protected by four functionally distinct populations of T cells, two resident and two recirculating, with differing territories of migration and distinct functional activities.
authors: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Rei
authors: R
authors: Watanabe
authors: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Ahmed
authors: A
authors: Gehad
authors: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Chao
authors: C
authors: Yang
authors: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Laura L
authors: LL
authors: Scott
authors: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Jessica E
authors: JE
authors: Teague
authors: Department of Dermatology, Inselspital, University of Bern, Bern, Switzerland.
authors: Christoph
authors: C
authors: Schlapbach
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Christopher P
authors: CP
authors: Elco
authors: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Victor
authors: V
authors: Huang
authors: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors: Tiago R
authors: TR
authors: Matos
authors: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Dana-Farber/Brigham and Women's Cancer Center, Boston, MA 02115, USA.
authors: Thomas S
authors: TS
authors: Kupper
authors: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Dana-Farber/Brigham and Women's Cancer Center, Boston, MA 02115, USA. rclark1@partners.org.
authors: Rachael A
authors: RA
authors: Clark
mesh_terms: D000074323:Alemtuzumab; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D037181:Lectins, C-Type / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010641:Phenotype; D012867:Skin / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D039001:Integrin alpha Chains; D007376:Interleukin-2; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C091367:alpha E integrins