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.
Highlights
Most autoimmune diseases (AID) have been shown to have a strong genetic component
Diabetes Onset after Rat Cytomegalovirus (RCMV) Infection In order to investigate whether RCMV influences the autoimmune process in DP-BB rats, animals were i.p. infected with 2 £ 106 pfu RCMV at 35 days of age
T Cell Subset Analysis In Vivo The effect of RCMV infection on T cell subsets was analyzed by performing flow cytometric analysis on both spleen and Peripheral Blood Mononuclear Cells (PBMNC) from DP and Diabetes resistant (DR)-BB rats after RCMV infection
Summary
Studies on monozygous twins showed, that only in 50% of the cases both siblings developed an AID of the same type (McFarland, 1992; Kumar et al, 1993). These data indicate that while AID occur in genetically susceptible individuals, many other factors must be involved in the phenotypic expression of autoimmunity (Rouse and Deshpande, 2002). Such non-genetic factors are environmental components, dietary constituents and infectious agents, viruses. 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
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