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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.

Original publication




Journal article



Publication Date





1415 - 1422


Adoptive Transfer, Aging, Animals, CD4-Positive T-Lymphocytes, Cytokines, Diabetes Mellitus, Type 1, Lymphocyte Activation, Mice, Mice, Inbred NOD, Mice, SCID, Receptors, Interleukin-2, Spleen, T-Lymphocytes