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Clinical and Developmental Immunology
Volume 10 (2003), Issue 2-4, Pages 133-139

Role of Peritoneal Macrophages in Cytomegalovirus-induced Acceleration of Autoimmune Diabetes in BB-rats

1Faculty of Medical Sciences, Immunology Section, Department of Cell Biology, University of Groningen, A. Deusinglaan 1, Groningen NL-9713 AV, The Netherlands
2Department of Medical Microbiology, University Hospital Maastricht, P. Deleyelaan 25, Maastricht NL-6202 AZ, The Netherlands

Copyright © 2003 Hindawi Publishing Corporation. 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.


Background: As one of the natural perturbants, infection with cytomegalovirus (CMV) is believed to play a role in the development of Type I diabetes. Using the DP-BB rat model for autoimmune diabetes, we here report about possible mechanisms responsible for R(at)CMV-induced accelerated onset of diabetes.

Methods: Rats were i.p. infected with 2 × 106 plaque forming units (pfu) RCMV and followed for diabetes development. Presence of RCMV antigens and DNA was analyzed by immunohistochemistry and PCR on pancreatic tissue and isolated islets. The effect of viral infection on peritoneal macrophages (pMΦ) and diabetes development was studied by analyzing numbers of pMΦ, virus permissiveness and by depletion of this subset by peritoneal lavage.

Results: RCMV accelerated onset of diabetes without infecting pancreatic islets. Immunohistochemistry and PCR on pancreas and isolated islets indicated that islets are non-permissive for RCMV. Infection results in an influx of pMΦ 1 day p.i. of which ~0.05% showed signs of reproductive infection. Depletion of pMΦ on days 1-3 p.i. completely counteracted the accelerating effect of RCMV.

Interpretation: RCMV accelerates onset of diabetes without infecting pancreatic islets. pMΦ might function as an carriage to disseminate virus to the pancreas where they enhance activation of autoreactive T cells resulting in accelerated onset of diabetes.