Autoimmune diabetes onset results from qualitative rather than quantitative age-dependent changes in pathogenic T-cells

S You, M Belghith, S Cobbold, MA Alyanakian… - Diabetes, 2005 - Am Diabetes Assoc
S You, M Belghith, S Cobbold, MA Alyanakian, C Gouarin, S Barriot, C Garcia, H Waldmann
Diabetes, 2005Am Diabetes Assoc
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)-β–dependent. Our present results suggest …
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)-β–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-β–dependent mediated inhibition. We propose that progression to overt disease correlates with the pathogenic T-cell’s escape from TGF-β–dependent T-cell–mediated regulation.
Am Diabetes Assoc