Immunological aspects of 'fulminant type 1 diabetes'.
'Fulminant diabetes' has been recognized as a super-acute onset and non-autoimmune type 1 diabetes. To evaluate autoimmunity against pancreatic beta cell in fulminant diabetes, ELISPOT assay was applied to the peripheral blood of these patients. In our ELISPOT system, GAD65-reactive and insulin B9-23-reactive IFN-gamma spots were detected in 46.3 and 26.0% of autoantibody-positive type 1 diabetes. Also, in fulminant type 1 diabetic patients, IFN-gamma spots in response to GAD65 and insulin B9-23 peptide were detected in 69.2 and 25.0%, respectively. These results suggest that anti-beta cell autoimmunity contributes to develop fulminant type 1 diabetes. Fulminant type 1 diabetes is known to have IDDM-resistant HLA DR2 with similar frequency of non-T1D subjects. In a mouse model, when islet-reactive CD8 cells are transferred to young NOD mice, the recipients develop overt diabetes within 1 week with massive insulitis. In (NOD x Balb/c) F1 mice, which hold idd-resistant genes, transfer of islet-reactive CD8 cells induced diabetes to 60% F1 recipients within 1 week with the later disappearance of insulitis. This mouse model shows very similar feathers to fulminant type 1 diabetes; idd-resistant HLA and no insulitis. These results implicated that once anti-islet immunity is optimally activated, subjects with partially resistant alleles could become overt diabetes.
Nagata
Masao
M
Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. nagata@med.kobe-u.ac.jp
Moriyama
Hiroaki
H
Kotani
Reiko
R
Yasuda
Hisafumi
H
Kishi
Minoru
M
Kurohara
Midori
M
Hara
Kenta
K
Yokono
Koichi
K
D000208:Acute Disease; D000818:Animals; D002096:C-Peptide / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000652:urine; D016883:Diabetic Ketoacidosis / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology
D002096:C-Peptide