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

Viveka Oling; Helena Reijonen; Olli Simell; Mikael Knip; Jorma Ilonen

doi:10.1016/j.cellimm.2011.12.008

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.

Authors

Viveka Oling¹, Helena Reijonen, Olli Simell, Mikael Knip, Jorma Ilonen

Affiliation

¹ Immunogenetics Laboratory, University of Turku, Medicity, Finland. viveka.oling@utu.fi

PMID: 22270037
DOI: 10.1016/j.cellimm.2011.12.008

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