title: Acceleration of type 1 diabetes by a coxsackievirus infection requires a preexisting critical mass of autoreactive T-cells in pancreatic islets.
abstract: 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.
authors.affiliation: Jackson Laboratory, Bar Harbor, Maine 04609, USA. dvs@jax.org
authors.forename: D V
authors.initials: DV
authors.lastname: Serreze
authors.forename: E W
authors.initials: EW
authors.lastname: Ottendorfer
authors.forename: T M
authors.initials: TM
authors.lastname: Ellis
authors.forename: C J
authors.initials: CJ
authors.lastname: Gauntt
authors.forename: M A
authors.initials: MA
authors.lastname: Atkinson
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D003384:Coxsackievirus Infections / Q000150:complications*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010179:Pancreas / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors