Determinants of susceptibility to the induction of autoimmune diabetes in inbred strains of rats

: Interleukin 2 (IL 2) proved to be important for the generation of autoreactive T cells in the pathogenesis of different autoimmune disorders, including diabetes. Also, we have previously shown that lymphoid cells obtained from inbred strains of rats Dark August (DA) and Albino Oxford (AO) exhibited a genetically determined difference in their ability to produce IL 2. In this study, in DA and AO rats, we analysed the susceptibility to the induction of autoimmune diabetes with multiple subdiabetogenic doses of alloxan. Rats were injected i.v. with 25 mg/kg b.w. of alloxan in 5 consecutive days. All DA rats developed moderate and persistent hyperglycaemia 15 days after the induction. In contrast, AO rats failed to develop the disease after the same regimen of induction. When the induction was made in (AO x DA)F1 rats, all of them developed the disease similar to the susceptible parental DA strain. However, the onset was delayed (the 40th day after the induction) and the glycaemia was constantly lower than in DA rats. Our results indicate that the difference in the response to the induction of autoimmune diabetes between susceptible DA strain, being high IL 2 producer, and resistant AO strain, being low IL 2 producer, is genetically determined. The results also suggest that this control could involve the gene determining the level of IL 2 production in DA and AO rats, thus signifying that the susceptibility to the induction of this form of autoimmune diabetes could be related to the level of IL 2 activity.