Murine gammaherpesvirus-68 infection alters self-antigen presentation and type 1 diabetes onset in NOD mice.
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.
Smith
Katherine A
KA
Department of Pathology, University of Cambridge, Cambridge, UK.
Efstathiou
Stacey
S
Cooke
Anne
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D004705:Endocytosis / Q000276:immunology; D005260:Female; D018142:Gammaherpesvirinae / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000821:virology
D016753:Interleukin-10