Cytomegalovirus Infection Modulates Cellular Immunity in an Experimental Model for Autoimmune Diabetes

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.