Modulation of low-dose streptozotocin-induced diabetes in mice by administration of antibodies to I-A, I-E and I-J determinants.

In male mice of strains C3H and C57BL/6 an experimental immune-mediated diabetes can be induced by multiple low doses of streptozotocin. The delay and partial suppression of hyperglycaemia after anti-I-A monoclonal antibody administration was dose dependent. Even saturation levels of anti-I-A did not cause complete protection from diabetes development. Administration of anti-I-E monoclonal antibody also significantly delayed the onset of hyperglycaemia. Surprisingly, the combined treatment with anti-I-A and anti-I-E did not result in better protection from diabetes. Thus, there is an I-A and I-E independent component of the disease. Furthermore, there is no restriction to either I-A or I-E. Anti-I-A was only effective when given at the beginning of the experiment, which implies that I-A molecules have a primary function during the induction of diabetes. The contribution of I-J to the disease process is different. Administration of a polyspecific alloantiserum to I-J almost completely prevented hyperglycaemia. Injections of monospecific antibodies to I-J determinants enhanced hyperglycaemia, especially when given after the induction of diabetes. This indicates that I-J is involved in initial as well as in later stages of the disease process.