Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects.
Glutamic acid decarboxylase 65 (GAD65) is a putative autoantigen associated with the pathogenesis of type 1 diabetes (T1D). The prevalence of autoreactive CD4+ T cells towards the immunodominant GAD65(555-567) epitope in DR4 healthy and T1D subjects was investigated with class II tetramers. A slightly higher percentage of diabetic subjects had GAD65(555-567) tetramer-positive T cells upon GAD65(555-567) peptide stimulation on the total CD4+ T-cell populations compared to healthy subjects. In contrast, three quarters of subjects in both groups had tetramer-positive T cells resulting from stimulation of the CD4+CD25+ regulatory T-cell depleted CD4+ T cells. The frequencies and TCR Vbeta gene usages of GAD65(555-567) T cells were also similar in both groups. Experiments demonstrated that GAD65(555-567)-reactive T cells in healthy and diabetic subjects had different CD45RA phenotypes. For the healthy group, GAD65(555-567)-reactive T cells were generally found in the CD45RA+ naïve T-cell pool while GAD65(555-567)-reactive T cells from T1D subjects were present in both CD45RA+ naïve and CD45RA- memory T-cell pools. These findings suggested that there is no difference in thymic selection of DR4 restricted GAD-reactive T cells amongst healthy and T1D individuals but GAD65(555-567)-reactive T cells have been preferentially activated in diabetic patients.
Danke
Nancy A
NA
Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, WA 98101, USA.
Yang
Junbao
J
Greenbaum
Carla
C
Kwok
William W
WW
D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology*; D015804:HLA-DR4 Antigen / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000473:pathology
D018984:Epitopes, T-Lymphocyte; D015804:HLA-DR4 Antigen; D016056:Immunodominant Epitopes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2