title: Skin CD4(+) memory T cells exhibit combined cluster-mediated retention and equilibration with the circulation.
abstract: Although memory T cells within barrier tissues can persist as permanent residents, at least some exchange with blood. The extent to which this occurs is unclear. Here we show that memory CD4(+) T cells in mouse skin are in equilibrium with the circulation at steady state. These cells are dispersed throughout the inter-follicular regions of the dermis and form clusters with antigen presenting cells around hair follicles. After infection or administration of a contact sensitizing agent, there is a sustained increase in skin CD4(+) T-cell content, which is confined to the clusters, with a concomitant CCL5-dependent increase in CD4(+) T-cell recruitment. Skin CCL5 is derived from CD11b(+) cells and CD8(+) T cells, with the elimination of the latter decreasing CD4(+) T-cell numbers. These results reveal a complex pattern of tissue-retention and equilibration for CD4(+) memory T cells in skin, which is altered by infection and inflammation history.
authors.affiliation: Department of Microbiology and Immunology; Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Collins
authors.affiliation: Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Microbiology and Immunology; Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Ali
authors.initials: A
authors.lastname: Zaid
authors.affiliation: Department of Microbiology and Immunology; Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Macleod
authors.affiliation: Department of Microbiology and Immunology; Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Chang Ook
authors.initials: CO
authors.lastname: Park
authors.affiliation: Malaria Immunology Laboratory, QIMR Berghofer Medical Research Institute and Australian Infectious Diseases Research Centre, The University of Queensland, Queensland 4006, Australia.
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
authors.affiliation: Department of Microbiology and Immunology; Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Sammy
authors.initials: S
authors.lastname: Bedoui
authors.affiliation: Department of Microbiology and Immunology; Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.affiliation: Department of Microbiology and Immunology; Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Mueller
authors.affiliation: Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kupper
authors.affiliation: Department of Microbiology and Immunology; Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gebhardt
authors.affiliation: Department of Microbiology and Immunology; Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018946:Chemokine CCL5 / Q000378:metabolism; D005260:Female; D018859:Hair Follicle / Q000166:cytology / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology / Q000473:pathology; D018259:Herpesvirus 1, Human; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008875:Middle Aged; D012867:Skin / Q000166:cytology / Q000276:immunology; D055815:Young Adult
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D007371:Interferon-gamma