Diversity of regulatory CD4+T cells controlling distinct organ-specific autoimmune diseases.
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.
Alyanakian
Marie-Alexandra
MA
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.
You
Sylvaine
S
Damotte
Diane
D
Gouarin
Christine
C
Esling
Anne
A
Garcia
Corinne
C
Havouis
Séverine
S
Chatenoud
Lucienne
L
Bach
Jean-François
JF
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
D001323:Autoantibodies; D013954:Thyroglobulin; D017506:H(+)-K(+)-Exchanging ATPase