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Murine Gammaherpesvirus-68 Infection Alters Self-Antigen Presentation and Type 1 Diabetes Onset in NOD Mice¹

Department of Pathology, University of Cambridge, Cambridge, United Kingdom

Recent research in line with the "hygiene hypothesis" has implicated virus infection in the delay or prevention of autoimmunity in murine models of type 1 diabetes such as the NOD mouse. We found that intraperitoneal or intranasal infection of NOD mice with the murine gammaherpesvirus-68 (MHV-68) significantly delayed diabetes onset in an age-dependent manner. The acute phase following intraperitoneal infection was associated with significantly reduced trafficking of autoreactive BDC2.5NOD CD4⁺ T cells to the pancreas but not the pancreatic lymph node (PLN); this was not as a result of MHV-68 M3 pan-chemokine binding protein expression. Autoreactive BDC2.5NOD CD4⁺ T cells within the PLN of MHV-68 infected mice were significantly more naive and proliferated to a lesser extent than those cells within the PLN of uninfected mice. These changes in autoreactive CD4⁺ T cell activation were associated with reduced dendritic cell endocytosis and soluble Ag presentation but were not as a result of virally induced IL-10 or changes in Ag-specific regulatory T cell populations.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ We are grateful to the Wellcome Trust for the support of this research and provision of grant support for K.A.S.

² Address correspondence and reprint requests to Professor Anne Cooke, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom. E-mail address: ac{at}mole.bio.cam.ac.uk

³ Abbreviations used in this paper: T1D, type 1 diabetes; MHV-68, murine gammaherpesvirus-68; DC, dendritic cells; PLN, pancreatic lymph nodes; BHK-21, baby hamster kidney-21; PFU, plaque-forming units; LCMV, lymphocytic choriomeningitis virus; i.n., intranasal; KRV, Kilham rat virus.