title: Diversity of regulatory CD4+T cells controlling distinct organ-specific autoimmune diseases.
abstract: Depletion of selected regulatory CD4+ T cell subsets induces the spontaneous onset of various immune or autoimmune disorders. It is not clear, however, whether a given subset, notably CD4+CD25+ regulatory T cells, protects from a wide spectrum of immune disorders, or whether specialized subsets of regulatory T cells control each given disease or group of diseases. We report here, using diabetes prone nonobese diabetic (NOD) mice, that depending on the regulatory T cells that are depleted, i.e., CD25+, CD62L+, or CD45RB(low), distinct immune diseases appear after transfer into NOD severe combined immunodeficiency (SCID) recipients. Thus, reconstitution of NOD SCID mice with CD25- T cells induces major gastritis and late-onset diabetes, but no or mild colitis. Reconstitution with CD62L- T cells induces fulminant diabetes with no colitis or gastritis. Reconstitution with CD45RB(high) T cells induces major colitis with wasting disease and no or very moderate gastritis and diabetes. Major differences among the three regulatory T cell subsets are also seen in vitro. The bulk of suppressor cells inhibiting the proliferation of CD4+CD25- T cells in coculture is concentrated within the CD25+ but not the CD62L+ or CD45RB(low) T cell subsets. Similarly, cytokine production patterns are significantly different for each regulatory T cell subset. Collectively, these data point to the diversity and organ selectivity of regulatory T cells controlling distinct autoimmune diseases whatever the underlying mechanisms.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U580, and Institut Fédératif Necker Enfants Malades, Faculté Necker Enfants Malades, 161 Rue de Sèvres, 75015 Paris, France.
authors.forename: Marie-Alexandra
authors.initials: MA
authors.lastname: Alyanakian
authors.forename: Sylvaine
authors.initials: S
authors.lastname: You
authors.forename: Diane
authors.initials: D
authors.lastname: Damotte
authors.forename: Christine
authors.initials: C
authors.lastname: Gouarin
authors.forename: Anne
authors.initials: A
authors.lastname: Esling
authors.forename: Corinne
authors.initials: C
authors.lastname: Garcia
authors.forename: Séverine
authors.initials: S
authors.lastname: Havouis
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bach
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000145:classification / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000276:immunology; D017506:H(+)-K(+)-Exchanging ATPase / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010179:Pancreas / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology
chemical_list: D001323:Autoantibodies; D013954:Thyroglobulin; D017506:H(+)-K(+)-Exchanging ATPase