Restricted TCR V beta gene expression and enterovirus infection in Type I diabetes: a pilot study

Aims/hypothesis. High frequencies of T-cell receptor (TCR) V beta7(+) T cel ls were detected among the lymphocytes isolated from pancreatic islets of c hildren at the onset of Type I (insulin-dependent) diabetes mellitus. We as sessed whether a preferential expression of certain TCR V beta gene familie s could also be detected among the peripheral blood mononuclear cells from diabetic patients. Methods. T-cell receptor repertoires were evaluated by using a semi-quantit ative RT-PCR-based technique and confirmed by FAGS analysis in peripheral b lood mononuclear cells from diabetic patients before, at and after onset of the disease. These patients were also tested for exposure to enteroviruses by RT-PCR and by measuring titres of enterovirus-specific antibodies of th e ISA, IgG, and IgM classes. Results. T-cell. receptor V beta7 gene family values were higher in recentl y-diagnosed diabetic patients (10.5% +/- 3.7) than in age-matched non-diabe tic controI subjects (5.1% +/- 1.6) (p <0.001). In a timecourse analysis of people who developed diabetes during clinical monitoring (i.e., converters ), T-cell receptor V<beta>7 gene expression showed values consistently abov e 10% (p < 0.0005). Long-standing diabetic patients showed lower percentage of V<beta>7 expression compared to values measured at disease onset. In th e longitudinal study of the converters, multiple acute enterovirus infectio ns were also detected. These infections appeared to be temporally related t o increased percentage of V beta7 gene transcripts. Conclusion/interpretation. The deviation in the T-cell receptor V beta repe rtoire among circulating T cells from diabetic patients seems to re-emphasi ze the importance of enterovirus infections in accelerating the progression of Type I diabetes.