Diabetes, Vol 49, Issue 5 708-711, Copyright © 2000 by American Diabetes Association

ARTICLES

Acceleration of type 1 diabetes by a coxsackievirus infection requires a preexisting critical mass of autoreactive T-cells in pancreatic islets

DV Serreze, EW Ottendorfer, TM Ellis, CJ Gauntt and MA Atkinson
Jackson Laboratory, Bar Harbor, Maine 04609, USA. dvs@jax.org

Coxsackievirus infections have been proposed as an environmental trigger for the development of T-cell-mediated autoimmune (type 1) diabetes by either providing a molecular mimic of the candidate pancreatic beta-cell autoantigen GAD or inducing bystander inflammation in the pancreas. In this study in the NOD mouse model, we found that infection with a pancreatrophic coxsackievirus isolate can accelerate type 1 diabetes development through the induction of a bystander activation effect, but only after a critical threshold level of insulitic beta-cell-autoreactive T-cells has accumulated. Thus, coxsackievirus infections do not appear to initiate beta-cell autoreactive immunity but can accelerate the process once it is underway. These findings indicate that the timing of a coxsackievirus infection, rather than its simple presence or absence, may have important etiological implications for the development of T-cell-mediated autoimmune type 1 diabetes in humans.
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