Cytomegalovirus infection modulates cellular immunity in an experimental model for autoimmune diabetes.
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 x 10(6) plaque forming units (pfu) RCMV. Diabetes development was monitored by frequent blood-glucose analysis. Effects of RCMV on CD4+, CD8+ and Vbeta-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. Vbeta-TCR percentages did not change upon RCMV-infection or RCMV-restimulation.


CONCLUSIONS
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.
van der Werf
Nienke
N
Faculty of Medical Sciences, Department of Cell Biology, Immunology Section, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Hillebrands
Jan-Luuk
JL
Klatter
Flip A
FA
Bos
Ineke
I
Bruggeman
Cathrien A
CA
Rozing
Jan
J
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology