The M variant of the encephalomyocarditis (EMC) virus uniquely infects the islets of Langerhans of mice causing necrosis and mononuclear cell inflammation. As a result, glucose intolerance develops resulting in a disease which resembles human type I insulin-dependent diabetes mellitus. Type I diabetes mellitus in man is believed to be associated with an immunopathological process, at least in some patients. It has been suggested that a virus could stimulate the immune response. Previous investigators have attempted to determine whether or not an immune process occurs in animals infected with the EMC virus, but results from various laboratories have differed. Our results indicate genetic factors are critical. We have found that in some strains of mice (DBA-2) the diabetes is solely or largely due to viral injury to the islets, whereas in others, (Balb/cby) viral injury is associated with an immunopathologic process. The mechanisms of immune injury will be explored using inbred strains of mice. The basic experimental approach employs lymphocyte depleted animals and adoptive transfer of various cellular elements. We will determine whether or not cytolytic T cells and macrophages play a role in the process and whether suppressor cells are active in animals which fail to develop immune diabetes. Studies also will focus on helper T cells and their possible role in stimulating a humoral antibody response which would result either in antibody-dependent, cell-mediated injury or beta cell injury due to complement-dependent cytolysis. Work with animals will be supported by investigators using beta cell cultures to assess the interaction of immune cells with isolated beta cells. This investigation should elucidate the immunopathologic processes which occur in mice consequent to virus infection of the islets of Langerhans and serve as a basis for future analyses of the genetic influence regulating the process.
| Babu, P G; Huber, S A; Craighead, J E (1986) Contrasting features of T-lymphocyte-mediated diabetes in encephalomyocarditis virus-infected Balb/cBy and Balb/cCum mice. Am J Pathol 124:193-8 |
| Huber, S A; Babu, P G; Craighead, J E (1985) Genetic influences on the immunologic pathogenesis of encephalomyocarditis (EMC) virus-induced diabetes mellitus. Diabetes 34:1186-90 |
| Babu, P G; Huber, S; Sriram, S et al. (1985) Genetic control of multisystem autoimmune disease in encephalomyocarditis virus infected BALB/cCUM and BALB/cBYJ mice. Curr Top Microbiol Immunol 122:154-61 |
| Babu, P G; Huber, S A; Craighead, J E (1985) Immunology of viral diabetes. Surv Synth Pathol Res 4:1-7 |
