<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p><italic>Background</italic>: 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.</p> <p><italic>Methods</italic>: Diabetes prone (DP)- and Diabetes resistant (DR)-BB rats were infected with 2 × 10<sup>6</sup> plaque forming units (pfu) RCMV. Diabetes development was monitored by frequent blood-glucose analysis. Effects of RCMV on CD4<sup>+</sup>, CD8<sup>+</sup> and Vβ-TCR<sup>+</sup> T-cell subsets were measured <italic>in vivo</italic>, and <italic>in vitro</italic> after restimulation with RCMV-infected fibroblasts. Proliferative capacity was determined by <sup>3</sup>H-Thymidine incorporation.</p> <p><italic>Results</italic>: RCMV-infection resulted in a significant acceleration of diabetes onset in DP-BB rats ( p=0.003). Percentages CD4<sup>+</sup> and CD8<sup>+</sup> T-cells were not affected <italic>in vivo</italic>. <italic>In vitro</italic>, RCMV-restimulation resulted in a decreased CD4<sup>+</sup>/CD8<sup>+</sup> 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.</p> <p><italic>Interpretation</italic>: RCMV-restimulation of splenic T-cells <italic>in vitro</italic> resulted in a strong RCMV-specific proliferation, probably also including autoreactive T-cells. <italic>In vivo</italic>, this polyclonal response might be involved in the observed accelerated diabetes development in DP-BB rats upon RCMV-infection.</p>
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Clin Dev Immunol. 2003 Jun-Dec; 10(2-4):153-160