title: Mouse and human CD8(+) CD28(low) regulatory T lymphocytes differentiate in the thymus.
abstract: Regulatory T (Treg) lymphocytes play a central role in the control of immune responses and so maintain immune tolerance and homeostasis. In mice, expression of the CD8 co-receptor and low levels of the co-stimulatory molecule CD28 characterizes a Treg cell population that exerts potent suppressive function in vitro and efficiently controls experimental immunopathology in vivo. It has remained unclear if CD8(+) CD28(low) Treg cells develop in the thymus or represent a population of chronically activated conventional T cells differentiating into Treg cells in the periphery, as suggested by their CD28(low) phenotype. We demonstrate that functional CD8(+) CD28(low) Treg cells are present in the thymus and that these cells develop locally and are not recirculating from the periphery. Differentiation of CD8(+) CD28(low) Treg cells requires MHC class I expression on radioresistant but not on haematopoietic thymic stromal cells. In contrast to other Treg cells, CD8(+) CD28(low) Treg cells develop simultaneously with CD8(+) CD28(high) conventional T cells. We also identified a novel homologous naive CD8(+) CD28(low) T-cell population with immunosuppressive properties in human blood and thymus. Combined, our data demonstrate that CD8(+) CD28(low) cells can develop in the thymus of mice and suggest that the same is true in humans.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) U1043, Toulouse, France.|Centre National de la Recherche Scientifique (CNRS) U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Yirajen
authors.initials: Y
authors.lastname: Vuddamalay
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) U1043, Toulouse, France.|Centre National de la Recherche Scientifique (CNRS) U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Attia
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) U1043, Toulouse, France.|Centre National de la Recherche Scientifique (CNRS) U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Rita
authors.initials: R
authors.lastname: Vicente
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) U1043, Toulouse, France.|Centre National de la Recherche Scientifique (CNRS) U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Pomié
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) U1043, Toulouse, France.|Centre National de la Recherche Scientifique (CNRS) U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Enault
authors.affiliation: Department of Pediatric Cardiology and Cardiovascular surgery, Children Hospital, University Hospital of Toulouse, Toulouse, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Leobon
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) U1043, Toulouse, France.|Centre National de la Recherche Scientifique (CNRS) U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Joffre
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) U1043, Toulouse, France.|Centre National de la Recherche Scientifique (CNRS) U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Paola
authors.initials: P
authors.lastname: Romagnoli
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm) U1043, Toulouse, France.|Centre National de la Recherche Scientifique (CNRS) U5282, Toulouse, France.|Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Joost P M
authors.initials: JP
authors.lastname: van Meerwijk
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology*
chemical_list: D018106:CD28 Antigens; D016827:CD8 Antigens
keywords: regulatory T lymphocytes; thymus; tolerance