Autoantigen-specific memory CD4+ T cells are prevalent early in progression to Type 1 diabetes

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.