title: Therapeutic potential of self-antigen-specific CD4+ CD25+ regulatory T cells selected in vitro from a polyclonal repertoire.
abstract: CD4+ CD25+ regulatory T cells (Treg) play a major role in the prevention of autoimmune diseases. Converging evidence indicates that Treg specific for self-antigens expressed by target tissues have a greater therapeutic potential than polyclonal Treg. Therefore, the selective expansion of rare self-antigen-specific T(reg) naturally present in a polyclonal repertoire of Treg is of major importance. In this work, we investigated the potential of different dendritic cell (DC) subsets to expand antigen-specific Treg in mice. The in vitro selective expansion of rare islet-specific Treg from polyclonal Treg could only be achieved efficiently by stimulation with CD8+ splenic DC presenting islet antigens. These islet-specific Treg exerted potent bystander suppression on diabetogenic T cells and prevented type 1 diabetes. This approach opens new perspectives for cell therapy of autoimmune diseases.
authors.affiliation: CNRS UMR 7087 and Université Pierre et Marie Curie, CERVI, Hôpital de la Pitié-Salpêtrière, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fisson
authors.forename: Fathia
authors.initials: F
authors.lastname: Djelti
authors.forename: Aurélie
authors.initials: A
authors.lastname: Trenado
authors.forename: Fabienne
authors.initials: F
authors.lastname: Billiard
authors.forename: Roland
authors.initials: R
authors.lastname: Liblau
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: José L
authors.initials: JL
authors.lastname: Cohen
authors.forename: Benoît L
authors.initials: BL
authors.lastname: Salomon
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D001324:Autoantigens; D015704:CD4 Antigens; D015375:Receptors, Interleukin-2