CONTRASTING FEATURES OF LYMPHOCYTE-T MEDIATED DIABETES IN ENCEPHALOMYOCARDITIS VIRUS-INFECTED BALB CBY AND BALB CCUM MICE

Abstract

Two closely related sublines of the Balb/c strain, Balb/cBy and Balb/cCum mice respond differently when inoculated with the diabetogenic M variant of the encephalomyocarditis (EMCM) virus. Although genetically similar, Balb/cBy mice develop severe hyperglycemia, whereas Balb/cCum animals exhibit only modest alterations in glucose tolerance. Virus concentrations in the pancreases of animals of both sublines are equivalent 3 days after inoculation and decrease rapidly to undetectable levels within 10 days, at a time when hyperglycemia in Balb/cBy mice peaks. These results support two conclusions: 1) direct virus-induced injury to the beta cells probably is not responsible for hyperglycemia in Balb/c mice, and 2) virus replication in the pancreas does not predict diabetes susceptibility. Diabetes in Balb/cBy mice is immunologically mediated. These animals generate cytolytic T lymphocytes specific for beta cells during periods corresponding to glucose intolerance, and anti-thymocyte serum treatment of infected mice prevents the development of hyperglycemia. The pathogenesis of diabetes in Balb/cCum mice is not clear. Although cytolytic T cells appear concomitant with glucose intolerance, anti-thymocyte serum has not consistently prevented the development of the metabolic disease.