A Molecular Approach for Development of Vaccines Against Cardiotropic and Pancreatropic Strains of Coxsackievirus B
Final rept. 1 Jan 2000-30 Jun 2001
CHILDREN'S HOSPITAL OF PITTSBURGH PA
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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.
- Medicine and Medical Research