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Intestinal T Lymphocytes of Different Rat Strains in Immunotoxicity

TNO Nutrition and Food Research Institute, Department of General Toxicology, Zeist, The Netherlands

Steven Spanhaak

TNO Nutrition and Food Research Institute, Department of General Toxicology, Zeist, The Netherlands

Joost P. Bruijntjes

TNO Nutrition and Food Research Institute, Department of General Toxicology, Zeist, The Netherlands

Carola P.P.C. Michielsen

Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

Joseph G. Vos

Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands, National Institute of Public Health and the Environment, Bilthoven, The Netherlands

C. Frieke Kuper

TNO Nutrition and Food Research Institute, Department of General Toxicology, Zeist, The Netherlands

In order to study the intestinal mucosal immune cells, with emphasis on single T lymphocytes, an inventory was made of single and organized lymphocytes in the epithelium and lamina propria of the small intestines of untreated Wistar, Fischer 344, and Lewis rats. The single and organized lymphocytes were examined microscopically. In addition, the single lymphocytes in the epithelium (IEL) and lamina propria (LPL) were analyzed by flow cytometry. Next, the use of flow cytometry analysis was explored to detect changes in the IEL T-lymphocyte population in subacute oral studies with the immunomodulating agents azathioprine and hexachlorobenzene. Untreated random-bred Wistar rats exhibited a large interindividual variability in IEL composition, while the variability was small in inbred Fischer 344 and Lewis rats. The explorative study with the 2 model immunomodulating compounds demonstrated that hexachlorobenzene increased the number of intraepithelial T lymphocytes with CD8+ phenotype at the cost of T cells with CD4+ phenotype in Lewis rats. Azathioprine did not induce distinct effects on the percentages of IEL. The data indicate that the intraepithelial lymphocytes in the intestines are a potential target for orally administered immunomodulating compounds and should therefore receive more attention in toxicologic pathology studies.

Key Words: Intraepithelial lymphocytes • lamina propria lymphocytes • gut mucosal immunity • azathioprine • hexachlorobenzene

Toxicologic Pathology, Vol. 27, No. 2, 171-179 (1999)
DOI: 10.1177/019262339902700204


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