title: Autoimmune diabetes onset results from qualitative rather than quantitative age-dependent changes in pathogenic T-cells.
abstract: Diabetogenic T-cells can be detected in pre-diabetic nonobese diabetic (NOD) mice after transfer in NOD-SCID recipients. Here we demonstrate that 6-week-old pre-diabetic NOD mice, >2 months before disease onset, already harbor pathogenic T-cells in equal numbers to overtly diabetic animals. The delay in diabetes appearance is explained by the presence of regulatory CD4+ CD25+ T-cells that control diabetogenic effectors and that are, in our hands, transforming growth factor (TGF)-beta-dependent. Our present results suggest, however, that diabetes onset is only partly explained by a decline in this regulatory T-cell activity. Another major factor appears to be the progressive resistance of diabetogenic cells to TGF-beta-dependent mediated inhibition. We propose that progression to overt disease correlates with the pathogenic T-cell's escape from TGF-beta-dependent T-cell-mediated regulation.
authors.affiliation: INSERM U580, Paris, France.
authors.forename: Sylvaine
authors.initials: S
authors.lastname: You
authors.forename: Mériam
authors.initials: M
authors.lastname: Belghith
authors.forename: Stephen
authors.initials: S
authors.lastname: Cobbold
authors.forename: Marie-Alexandra
authors.initials: MA
authors.lastname: Alyanakian
authors.forename: Christine
authors.initials: C
authors.lastname: Gouarin
authors.forename: Samia
authors.initials: S
authors.lastname: Barriot
authors.forename: Corinne
authors.initials: C
authors.lastname: Garcia
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bach
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
mesh_terms: D019264:Adoptive Transfer; D000375:Aging / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000097:blood; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D015375:Receptors, Interleukin-2