Evidence from twins for acquired cellular immune hyperactivity in type 1 diabetes.
Type 1 diabetes has been associated with an increased frequency of activated T cells and T-cell hyperactivity to non-specific and disease-specific stimuli including the islet autoantigen glutamic acid decarboxylase 65 (GAD). To address whether T-cell hyperactivity is genetic or acquired we measured whole blood cytokines in vitro in response to GAD or tetanus in 18 identical twin pairs, nine discordant for type 1 diabetes. In addition, the activity of 2', 5' oligoadenylate synthetase (OAS) in blood mononuclear cells was measured as a marker of viral infection. Interleukin-2 (IL-2) basally and IL-2 and interferon-gamma (IFN-gamma) in response to GAD, were detected more frequently and at higher levels in diabetic compared to non-diabetic twins. IL-10 was not different between groups. OAS activity was increased in diabetic compared to non-diabetic twins and showed a correlation with basal IL-2 and GAD-stimulated IFN-gamma and IL-10. These findings suggest that T-cell hyperactivity in type 1 diabetes is an acquired trait and could reflect persisting virus expression.
Petrovsky
Nikolai
N
Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Kyvik
Kirsten O
KO
Bonnevie-Nielsen
Vagn
V
Beck-Nielsen
Henning
H
Green
Anders
A
Harrison
Leonard C
LC
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D004200:Diseases in Twins; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D012042:Registries; D013745:Tetanus Toxoid / Q000276:immunology; D014430:Twins, Monozygotic; D014777:Virus Diseases / Q000276:immunology
D001324:Autoantigens; D015415:Biomarkers; D016207:Cytokines; D007376:Interleukin-2; D013745:Tetanus Toxoid; D015088:2',5'-Oligoadenylate Synthetase; D005968:Glutamate Decarboxylase