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

Cell Immunol. 2012;273(2):133-9. doi: 10.1016/j.cellimm.2011.12.008. Epub 2012 Jan 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / immunology
  • Autoantigens / immunology*
  • Autoimmunity
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Case-Control Studies
  • Child
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / physiopathology
  • Disease Progression
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / immunology*
  • Glutamate Decarboxylase / metabolism
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immune Tolerance*
  • Immunologic Memory*
  • Insulin / genetics
  • Insulin / immunology*
  • Insulin / metabolism
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Lymphocyte Activation / immunology
  • Polymerization

Substances

  • Autoantibodies
  • Autoantigens
  • Histocompatibility Antigens Class II
  • Insulin
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2