Summary
The NOD mouse, which shows many features of human IDDM, is extensively used to evaluate the role of T lymphocytes in the pathogenesis of autoimmune diabetes. The development of diabetes in this model appears to be controlled by a finely tuned immunoregulatory balance between autoaggressive T cells and regulatory immune phenomena, the disruption of which may result in destruction of insulin-secreting cells. The absolute requirement of sublethal irradiation to permit transfer of the disease to non-diabetic adult syngeneic mice provides indirect evidence for the presence of regulatory T cells in non-diabetic NOD mice. We have previously reported that the reconstitution of irradiated recipients by CD4 + T cells from nondiabetic female NOD mice blocks the transfer of diabetes by spleen cells from diabetic donors. We now report evidence that anti-CD4 monoclonal antibodies can substitute for irradiation in rendering adult NOD male mice susceptible to diabetes transfer by diabetogenic spleen cells. Efficient diabetes transfer can be achieved in non-irradiated adult NOD recipients provided they are thymectomized and CD4 + T-cell depleted prior to the transfer. The role of thymectomy is to limit T cell regeneration after anti-T cell monoclonal antibody challenge. Our data confirm that regulatory CD4 + T-cells, which efficiently counterbalance diabetogenic cells, are present in adult NOD male animals.
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Abbreviations
- FITC:
-
fluorescein isothiocynate
- HBSS:
-
Hank's balanced salt solution
- IDDM:
-
insulin-dependent diabetes mellitus
- IL:
-
interleukin
- NOD:
-
non-obese diabetic
- TH:
-
T helper
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Sempé, P., Richard, M.F., Bach, J.F. et al. Evidence of CD4 + regulatory T cells in the non-obese diabetic male mouse. Diabetologia 37, 337–343 (1994). https://doi.org/10.1007/BF00408468
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DOI: https://doi.org/10.1007/BF00408468