Detection of CD4+ autoreactive T cells in T1D using HLA class II tetramers.
The use of soluble class II MHC tetramers has enabled the identification of autoantigen-specific T cells in the peripheral blood of type 1 diabetes patients. Our approach takes advantage of the appearance of highly activated T cells expressing a CD25(+)/CD4(high+) phenotype induced by immobilized class II MHC monomer containing the GAD65 peptide. Almost all T cells that stain with the specific tetramer reside in this population and, since this activation profile is not present in normal subjects, it may provide a useful tool for analysis of the T cell response in autoimmune diabetes. The utilization of tetramer techniques in the detection of autoreactive T cells is a powerful tool to gain insight into mechanisms of the molecular basis of autoimmunity. The phenotyping of T cells should provide useful markers for progression of immune-mediated beta cell reactivity and can be utilized in clinical trials to evaluate the efficacy of the immunomodulatory therapies targeting intervention/prevention of autoimmune diseases.
Reijonen
Helena
H
Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101, USA. reijonen@benaroyaresearch.org
Kwok
William W
WW
Nepom
Gerald T
GT
D015704:CD4 Antigens / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II