Murine gammaherpesvirus-68 infection alters self-antigen presentation and type 1 diabetes onset in NOD mice.

Abstract

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.