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Department of Pathology and Immunology and Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110
Nonobese diabetic (NOD) mice carrying a transgenic TCR from an
islet Ag-specific CD4 T cell clone, BDC2.5, do not develop diabetes. In
contrast, the same transgenic NOD mice on the SCID background develop
diabetes within 4 wk after birth. Using a newly developed mAb specific
for the BDC2.5 TCR, we examined the interaction between diabetogenic T
cells and regulatory T cells in NOD.BDC transgenic mice. CD4 T cells
from NOD.BDC mice, expressing high levels of the clonotype, transfer
diabetes to NOD.SCID recipients. In contrast, CD4 T cells
expressing low levels due to the expression of both transgenic and
endogenous TCR 
-chains inhibit diabetes transfer. The clonotype-low
CD4 T cells appear late in the ontogeny in the thymus and peripheral
lymphoid organs, coinciding with resistance to cyclophosphamide-induced
diabetes. These results demonstrate that diabetic processes in NOD.BDC
mice are regulated by a balance between diabetogenic T cells and
regulatory T cells. In the absence of specific manipulation, regulatory
T cell function seems to be dominant and mice remain diabetes free.
Understanding of mechanisms by which regulatory T cells inhibit
diabetogenic processes would provide means to prevent diabetes
development in high-risk human populations.
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