This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Bruder, M. C. Articles by Kuper, C. F. Search for Related Content PubMed PubMed Citation Articles by Bruder, M. C. Articles by Kuper, C. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB AZATHIOPRINE HEXACHLOROBENZENE Social Bookmarking                         What's this?

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

References

• Cerf-Bensussan N., Quaroni A., Kurnick JT, and Bhan AK (1984). Intraepithelial lymphocytes modulate la expression by intestinal epithelial cells. J. Immunol. 132: 2244-2252.[Abstract]
• Ebert EC and Roberts AI (1995). Pitfalls in the characterization of small intestinal lymphocytes. J. Immunol. Methods 178: 219-227.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Elion GB and Hitchings GH (1975). Azathioprine. In: Handbook of Experimental Pharmacology, O Eichler, A Farah, H Herken, and AD Welch (eds). Springer-Verlag, New York, pp. 404-425.
• Fichtelius KE, Yunis EJ, and Good RA (1968). Occurrence of lymphocytes within the gut epithelium of normal and neonatally thymectomized mice. Proc. Soc. Exp. Biol. Med. 128: 185-188.[CrossRef][Medline] [Order article via Infotrieve]
• Fujihashi K., Taguchi T., McGhee JR, Eldridge JH, Bruce MG, Green DR. Singh B., and Kiyono H. (1990). Regulatory function for murine intraepithelial lymphocytes. Two subsets of CD3+, T cell receptor-1+ intraepithelial lymphocyte T cells abrogate oral tolerance. J. Immunol. 145: 2010-2019.[Abstract]
• Gyorffy EJ, Glogauer M., Kennedy L., and Reynolds JD (1992). T-cell receptor association with lymphocyte populations in sheep intestinal mucosa. Immunology 77: 25-30.[Web of Science][Medline] [Order article via Infotrieve]
• Heijden van der PJ and Stok W. (1987). Improved procedure for the isolation of functionally active lymphoid cells from the murine intestine. J. Immunol. Methods 103: 161-167.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• ICICIS Group Investigators ( 1998). Report of interlaboratory validation study of assessment of direct immunotoxicity in the rat. Toxicology. 125: 183-201.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• James SP and Zeitz M. (1994). Human gastrointestinal mucosal T cells. In: Handbook of Mucosal Immunology, PL Ogra, J Mesteckv, ME Lamm, W Strober, JR McGhee, and J Bienenstock (eds). Academic Press, San Diego, pp. 275-285.
• Jarry A., Cerf-Bensussan N., Brousse N., Selz F., and Guy-Grand D. (1990). Subsets of CD3+ (T cell receptor β or ) and CD3-lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood. Eur. J. Immunol. 20: 1097-1103.[Web of Science][Medline] [Order article via Infotrieve]
• Kagnoff MF (1996). Mucosal immunology: New frontiers. Immunol. Today 17: 57-59.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Kampinga J., Huls G., Dijk F., van Luyn M., and Kroese F. (1994). Description of Kampinga's Accumulations of Gut Associated Lymphoid-Like Cells (KAGALLs) Containing a New Cell Type Specific for the Mucosal Immune System. Proceedings of Thymus Workshop, April 24-27, 1994, in Rolduc, The Netherlands.
• Kawabata TT, Burleson GR, Ernst PB, and Ullrich SE (1990). Symposium overview. Immunotoxicology of regional lymphoid tissue: The respiratory and gastrointestinal tracts and skin. Fundam. Appl. Toxicol. 26: 8-19.
• Kfhnlein P., Park JH, Herrmann T., Elbe A., and Hunig T. (1994). Identification and characterization of rat T lymphocytes in peripheral lymphoid organs, small intestine and skin with a monoclonal antibody to a constant determinant of the T cell receptor. J. Immunol. 153: 979-986.[Abstract]
• Lefrançois L. (1991). Intraepithelial lymphocytes of the rat intestinal mucosa: Curiouser and curiouser. Semin. Immunol. 3: 99-108.[Medline] [Order article via Infotrieve]
• Lefrançois L. (1991). Phenotypic complexity of intraepithelial lymphocytes of the small intestine. J. Immunol. 147: 1746-1751.[Abstract]
• Lefrançois L. (1994). Basic aspects of intraepithelial lymphocyte immunobiology. In: Handbook of Mucosal Immunology, PL Ogra, J Mestecky, ME Lamm, JR McGhee, and J Bienenstock (eds). Academic Press, San Diego, pp. 287-297.
• Lefrançois L. and Puddington L. (1995). Extrathymic intestinal T-cell development: Virtual reality? Immunol. Today 16: 16-21.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Lillehoj HS and Chung KS (1992). Postnatal development of T-lymphocyte subpopulations in the intestinal intraepithelium and lamina propria in chickens. Vet. Immunol. Immunopathol. 31: 347-360.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Mayrhofer G. (1980). Thymus-dependent and thymus-independent subpopulations of intestinal intraepithelial lymphocytes: A granular subpopulation of probable bone marrow origin and relationship to mucosal mast cells. Blood 55: 532-535.[Abstract/Free Full Text]
• Michielsen Cppc, Bloksma N., Ultee A., van Mil F., and Vos JG (1997). Hexachlorobenzene-induced immunomodulation and skin and lung lesions: A comparison between Brown Norway, Lewis and Wistar rats. Toxicol. Appl. Pharmacol. 144: 12-26.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Moolenbeek C. and Ruitenberg EJ (1981). The "Swiss roll": A simple technique for histological studies of the rodent intestine. Lab. Anim. 15: 57-59.[Abstract/Free Full Text]
• Ogra PL, Mestecky J., Lamm ME, Strober W., McGhee JR, and Bienenstock J. (1994). Handbook of Mucosal Immunology. Academic Press, San Diego.
• Rocha B., Vassali P., and Guy-Grand D. (1991). The Vβ repertoire of mouse gut homodimeric CD8+ intraepithelial T cell receptor β + lymphocytes reveals a major extrathymic pathway of T cell differentiation. J. Exp. Med. 173: 483-486.[Abstract/Free Full Text]
• Rothkötter HJ, Ulbrich H., and Pabst R. (1991). The postnatal development of gut lamina propria lymphocytes: Number, proliferation, and T and B cell subsets in conventional and germ-free pigs. Pediatr. Res. 29: 237-242.[Web of Science][Medline] [Order article via Infotrieve]
• Schuurman HJ, Krajnc-Franken Mam, Kuper CF, van Loveren H., and Vos JG (1991). Immune system. In: Handbook of Toxicologic Pathology, WM Haschek and CG Rousseaux (eds). Academic Press, New York, pp. 421-487.
• Takimoto H., Nakamura T., Takeuchi M., Sumi Y., Tanaka T., Nomuto K., and Yoshikai Y. (1992). Age-associated increase in number of CD4+CD8+ intestinal intraepithelial lymphocytes in rats. Eur. J. Immunol. 22: 159-164.[Web of Science][Medline] [Order article via Infotrieve]
• Torres-Nagel NE, Kraus E., Brown MH, Tiefenthaler G., Mitnacht R. Williams AF, and Hunig T. (1992). Differential thymus dependence of rat CD8 isoform expression. Eur. J. Immunol. 22: 2841-2848.[Web of Science][Medline] [Order article via Infotrieve]
• Vaage TJ, Dissen E., Ager A., Roberts I., Fossum S., and Rolstad B. (1990). T cell receptor-bearing cells among rat intestinal intraepithelial lymphocytes are mainly β + and are thymus dependent. Eur. J. Immunol. 20: 1193-1196.[Web of Science][Medline] [Order article via Infotrieve]
• Vos JG, van Logten MJ, Kreeftenberg JG, and Kruizinga W. (1979). Hexachlorobenzene-induced stimulation of the humoral immune response in rats. Ann. NY Acad. Sci. 320: 535-550.[Medline] [Order article via Infotrieve]

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


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. F. Kuper, M. Van Zijverden, C. Klaassen, M. Tegelenbosch-Schouten, and A. P.M. Wolterbeek Effects of Cyclosporin A and Cyclophosphamide on Peyer's Patches in Rat, Exposed in utero and Neonatally or During Adult Age Toxicol Pathol, February 1, 2007; 35(2): 226 - 232. [Abstract] [Full Text] [PDF]

				M. F. Cesta Normal Structure, Function, and Histology of Mucosa-Associated Lymphoid Tissue Toxicol Pathol, August 1, 2006; 34(5): 599 - 608. [Abstract] [Full Text] [PDF]

				C. F. Kuper, J. H. Harleman, H. B. Richter-Reichelm, and J. G. Vos Histopathologic Approaches to Detect Changes Indicative of Immunotoxicity Toxicol Pathol, May 1, 2000; 28(3): 454 - 466. [Abstract] [PDF]

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Bruder, M. C. Articles by Kuper, C. F. Search for Related Content PubMed PubMed Citation Articles by Bruder, M. C. Articles by Kuper, C. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB AZATHIOPRINE HEXACHLOROBENZENE Social Bookmarking                         What's this?