Induction of virus-induced IDDM in virus resistant mice without lymphocyte maturation.
The role of lymphocytes in the pathogenesis of viral-induced insulin dependent diabetes mellitus (IDDM) is controversial. To better understand how a virus-induced IDDM depends on the infiltrating lymphocytes, encephalomyocarditis virus (EMCV) was inoculated intraperitoneally into three kinds of mice; virus-susceptible C57BL/6, virus-resistant 129/SV and recombination activity gene-2 (Rag2) knockout 129/SV mice. Pancreatic inflammation and beta cell necrosis were evaluated after EMCV, D variant (10(3) pfu/mouse) inoculation. On post-inoculation day 14, the lethal rates of C57BL/6, 129/SV and Rag2 knockout mice were 52, 10 and 100%, respectively. The blood glucose in Rag2KO mice on day 8 was significantly elevated as compared with 129SV mice (231 +/- 49 vs 169 +/- 32 mg/dl, P<0.05). In situ hybridization demonstrated the EMCV genome in the pancreas of Rag2 knockout and C57BL/6 mice, but not in 129/SV mice. Beta cell necrosis were more severe in Rag-2 knockout mice than in wild type 129/SV mice, but lymphocyte infiltration was less severe than C57BL/6. Pancreas in Rag2 knockout mice infected with virus were affected more severely than the virus-resistant strain of mice. Diabetogenic virus induced IDDM in virus-resistant mice without mature lymphocytes.
Department of Laboratory Medicine, Gunma University School of Medicine, Gunma University, Maebashi, Japan. kanda@sb.gunma-u.ac.jp
T
T
Kanda
T
T
Utsugi
S
S
Kawazu
J E
JE
Wilson
D
D
Yang
A
A
Suarez
B M
BM
McManus
R
R
Nagai
I
I
Kobayashi
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D018188:Cardiovirus Infections / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D004686:Encephalomyocarditis virus; D005260:Female; D007113:Immunity, Innate; D017403:In Situ Hybridization; D007694:Killer Cells, Natural / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010179:Pancreas / Q000473:pathology / Q000821:virology
D000914:Antibodies, Viral; D001786:Blood Glucose