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Clin Dev Immunol. 2003 Jun-Dec; 10(2-4): 153–160.
PMCID: PMC2485415
Cytomegalovirus Infection Modulates Cellular Immunity in an Experimental Model for Autoimmune Diabetes
Nienke van der Werf,1 Jan-Luuk Hillebrands,1 Flip A. Klatter,1 Ineke Bos,1 Cathrien A. Bruggeman,2 and Jan Rozing1
1 Faculty of Medical Sciences, Department of Cell Biology, Immunology Section, University of Groningen, A. Deusinglaan 1, Groningen, AV, 9713, The Netherlands,
2 Department of Medical Microbiology, University Hospital Maastricht, P.O. Box 5800, Maastricht, AZ, 6202, The Netherlands,
Abstract
Background: Viral infections are thought to play a role in the development of autoimmune diseases like type 1 diabetes. In this study we investigated the effect of Rat Cytomegalovirus (RCMV) infection on cellular immunity in a well-defined animal model for diabetes, the Biobreeding (BB) rat.
Methods: Diabetes prone (DP)- and Diabetes resistant (DR)-BB rats were infected with 2 × 106 plaque forming units (pfu) RCMV. Diabetes development was monitored by frequent blood-glucose analysis. Effects of RCMV on CD4+, CD8+ and Vβ-TCR+ T-cell subsets were measured in vivo, and in vitro after restimulation with RCMV-infected fibroblasts. Proliferative capacity was determined by 3H-Thymidine incorporation.
Results: RCMV-infection resulted in a significant acceleration of diabetes onset in DP-BB rats ( p=0.003). Percentages CD4+ and CD8+ T-cells were not affected in vivo. In vitro, RCMV-restimulation resulted in a decreased CD4+/CD8+ blastoid T-cell ratio compared to ConA ( p=0.00028). Furthermore, RCMV-restimulation resulted in a strong RCMV-specific proliferation, which comprises about 50% of the response triggered by ConA. Vβ-TCR percentages did not change upon RCMV-infection or RCMV-restimulation.
Interpretation: RCMV-restimulation of splenic T-cells in vitro resulted in a strong RCMV-specific proliferation, probably also including autoreactive T-cells. In vivo, this polyclonal response might be involved in the observed accelerated diabetes development in DP-BB rats upon RCMV-infection.
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