title: Cutting edge: CD69 interference with sphingosine-1-phosphate receptor function regulates peripheral T cell retention.
abstract: Tissue-resident memory T cells provide local immune protection in barrier tissues, such as skin and mucosa. However, the molecular mechanisms controlling effector T cell retention and subsequent memory formation in those locations are not fully understood. In this study, we analyzed the role of CD69, an early leukocyte activation marker, in regulating effector T cell egress from peripheral tissues. We provide evidence that CD69 surface expression by skin-infiltrating CD8 T cells can be regulated at multiple levels, including local Ag stimulation and signaling through type I IFNRs, and it coincides with the transcriptional downregulation of the sphingosine-1-phosphate receptor S1P1. Importantly, we demonstrate that expression of CD69, by interfering with sphingosine-1-phosphate receptor function, is a critical determinant of prolonged T cell retention and local memory formation. Our results define an important step in the generation of long-lived adaptive immune memory at body surfaces.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia gebhardt@unimelb.edu.au lkmackay@unimelb.edu.au.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Mackay
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Asolina
authors.initials: A
authors.lastname: Braun
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Macleod
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Collins
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Christina
authors.initials: C
authors.lastname: Tebartz
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Sammy
authors.initials: S
authors.lastname: Bedoui
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia gebhardt@unimelb.edu.au lkmackay@unimelb.edu.au.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gebhardt
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000821:virology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D007370:Interferon Type I; D037181:Lectins, C-Type; D049349:Receptors, Lysosphingolipid; D000099192:CD69 Antigens