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Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects.

Abstract：

: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.

journal_name

J Autoimmun

journal_title

Journal of autoimmunity

authors

Danke NA,Yang J,Greenbaum C,Kwok WW

doi

10.1016/j.jaut.2005.08.007

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

303-11

issue

4

eissn

0896-8411

issn

1095-9157

pii

S0896-8411(05)00105-8

journal_volume

25

pub_type

杂志文章

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