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Intestinal T lymphocytes of different rat strains in immunotoxicity

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Author: Bruder, M.C. · Spanhaak, S. · Bruijntjes, J.P. · Michielsen, C.P.P.C. · Vos, J.G. · Kuper, C.F.
Institution: Centraal Instituut voor Voedingsonderzoek TNO
Source:Toxicologic Pathology, 2, 27, 171-179
Identifier: 235005
Keywords: Nutrition · Azathioprine · Gut mucosal immunity · Hexachlorobenzene · Intraepithelial lymphocytes · Lamina propria lymphocytes · Azathioprine · Hexachlorobenzene · Animal experiment · Blood toxicity · Cell count · Cell isolation · Controlled study · Drug effect · Drug targeting · Female · Flow cytometry · Gastrointestinal toxicity · Immunomodulation · Immunotoxicity · Intestine epithelium · Intestine mucosa · Male · Nonhuman · Oral drug administration · Priority journal · Rat · T lymphocyte · Animals · Azathioprine · Body Weight · CD4-CD8 Ratio · CD4-Positive T-Lymphocytes · CD8-Positive T-Lymphocytes · Female · Flow Cytometry · Hexachlorobenzene · Immunohistochemistry · Immunosuppressive Agents · Intestinal Mucosa · Intestines · Killer Cells, Natural · Lymphocyte Count · Male · Rats · Rats, Inbred F344 · Rats, Inbred Lew · Rats, Wistar · Receptors, Antigen, T-Cell, gamma-delta · Species Specificity · T-Lymphocytes · Animalia · Rattus norvegicus


In order to study the intestinal mucosal immune cells, with emphasis on single T lymphocytcs, 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 tIEL) 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 oft 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.