T cell responses to enterovirus antigens and to beta-cell autoantigens in unaffected children positive for IDDM-associated autoantibodies.
Enterovirus infections have been implicated in the pathogenesis of IDDM in a number of studies. The aim of the present study was to evaluate whether the cellular immune response to enterovirus antigens is abnormal in children who test positive for IDDM-associated autoantibodies. Lymphocyte proliferation responses were analysed to enterovirus antigens and to a panel of beta-cell autoantigen preparations in 31 non-diabetic ICA and/or GAD65 antibody-positive children and in 19 ICA/GAD65-negative control children. The responses to highly purified enteroviruses did not differ between autoantibody (AA)-positive and -negative subjects. However, proliferation responses to coxsackievirus-infected cell lysate, which also included non-structural proteins of the virus, were higher in AA-positive than in AA-negative subjects (P<0.05). This difference was most marked in children carrying the HLA-DQB1*02 allele (P=0.01). AA-positive subjects also had higher responses to one of the three GAD65 antigen preparations compared to AA-negative subjects (P<0.05). Proliferation responses to the adenovirus hexon protein did not differ between the groups. These results show that the increased responses to virus infected cell lysates are associated with early phases of beta-cell autoimmunity.
D000293:Adolescent; D000956:Antigens, Viral / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004770:Enterovirus / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*