title: Autoantigen-specific memory CD4+ T cells are prevalent early in progression to Type 1 diabetes.
abstract: Autoreactive CD4(+) T cells contribute to the destruction of insulin producing beta cells in Type 1 diabetes (T1D). Using MHC class II tetramers, we have analyzed the frequency of GAD65- (274-286; 555-567) and insulin- (A1-15; A6-21) specific CD4(+) T cells in 31 children with T1D, 65 multiple autoantibody-positive children and 93 HLA- and age-matched controls. In a smaller group of children T-cell responses of memory origin to the same autoantigens were investigated. We observed a higher response to GAD65 555-567 in the autoantibody-positive children than in the controls (P=0.017). Memory T-cell responses to GAD65 555-567 were more frequent among T1D patients (P=0.025) and autoantibody-positive (P=0.054), while all controls were negative (n=28). In summary, the presence of antigen experienced GAD65-specific T cells in the subjects with diabetes-associated autoimmunity is encouraging for further directions in the prediction of T1D.
authors.affiliation: Immunogenetics Laboratory, University of Turku, Medicity, Finland. viveka.oling@utu.fi
authors.forename: Viveka
authors.initials: V
authors.lastname: Oling
authors.forename: Helena
authors.initials: H
authors.lastname: Reijonen
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007156:Immunologic Memory; D007328:Insulin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D058105:Polymerization
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2