Induction of Autoimmune Disease by Depletion of Regulatory T Cells

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Organ-specific autoimmune diseases can be induced in rodents that do not normally spontaneously develop autoimmunity by using procedures that render the animals partially T cell deficient. Using a protocol of adult thymectomy followed by four doses of sublethal y irradiation, insulin-dependent diabetes can be induced in normal PVG.RT1u rats, an inbred congenic strain that has the same major histocompatibility complex (MHC) allotype as the spontaneously diabetic BB rat. Onset of the disease ranges from 3 to 18 weeks after the final dose of irradiation, with 98% of male and 70% of female animals becoming diabetic. The animals develop an acute and rapidly fatal syndrome with severe weight loss and hyperglycemia. Using this protocol, 50% to 60% of PVG.RT1u animals may develop anti-thyroid antibodies but they have no adverse effect. Female rats of the strain PVG.RTIc will also develop diabetes if treated by this protocol, but with a much lower incidence (10% to 53%).

This unit describes the induction of insulin-dependent diabetes in the rat (see Basic Protocol). A modified protocol allows for the induction of a more severe form of the disease (see Alternate Protocol).

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