INDUCTION OF VIRUS-INDUCED IDDM IN VIRUS RESISTANT MICE WITHOUT LYMPHOCYTE MATURATION

The role of lymphocytes in the pathogenesis of viral-induced insulin d ependent diabetes mellitus (IDDM) is controversial. To better understa nd how a virus-induced IDDM depends on the infiltrating lymphocytes, e ncephalomyocarditis virus (EMCV) was inoculated intraperitoneally into three kinds of mice; virus-susceptible C57BL/6, virus-resistant 129/S V and recombination activity gene-2 (Rag2) knockout 129/SV mice. Pancr eatic inflammation and beta cell necrosis were evaluated after EMCV, D variant (10(3) pfu/mouse) inoculation. On post-inoculation day 14, th e lethal rates of C57BL/6, 129/SV and Rag2 knockout mice were 52, 10 a nd 100%, respectively. The blood glucose in Rag2KO mice on day 8 was s ignificantly elevated as compared with 129SV mice (231 +/- 49 vs 169 /- 32 mg/dl, P<0.05). In situ hybridization demonstrated the EMCV geno me in the pancreas of Rag2 knockout and C57BL/6 mice, but not in 129/S V mice. Beta cell necrosis were more severe in Rag-2 knockout mice tha n in wild type 129/SV mice, but lymphocyte infiltration was less sever e than C57BL/6. Pancreas in Rag2 knockout mice infected with virus wer e affected more severely than the virus-resistant strain of mice. Diab etogenic virus induced IDDM in virus-resistant mice without mature lym phocytes.