A Molecular Approach for Development of Vaccines Against Cardiotropic and Pancreatropic Strains of Coxsackievirus B

Abstract : High frequencies of T-cell receptor (TCR) VBeta7+ T-cells are detected among lymphocytes isolated from pancreatic islets of children at the onset of Type 1 diabetes. Peripheral blood mononuclear cells from recently-diagnosed diabetic patients and from patients with diabetes from 2 to 14 years of duration were analyzed to assess whether a preferential expression could also be detected among them. TCR VBeta7 gene expression in patients who converted to diabetes while under our routine clinical monitoring, showed values (> 10%) consistently higher than those measured in age-matched non-diabetic controls (5.1% +/- 1.6) (p < 0.0005). Also, among the converters, multiple acute enterovirus infections were detected. These infections appeared to be temporally related with increase in levels of VBeta7 gene transcripts. These data demonstrate that a deviation in the TCR VBeta repertoire is present in circulating T-cells from diabetic patients during disease progression and reemphasize the importance of Coxsackievirus B infections in the etiology of Type 1 diabetes. If we will be able to recognize the segment of the protein that confers to CVB its VBeta7 gene triggering properties, we will be in the position of generating a vaccine that blocks the diabetogenic process mediated by the virus.