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. 1996 Oct;89(2):268–273. doi: 10.1046/j.1365-2567.1996.d01-740.x

Development and cytolytic function of intestinal intraepithelial T lymphocytes in antigen-minimized mice.

M Kawaguchi-Miyashita 1, K Shimizu 1, M Nanno 1, S Shimada 1, T Watanabe 1, Y Koga 1, Y Matsuoka 1, H Ishikawa 1, K Hashimoto 1, M Ohwaki 1
PMCID: PMC1456489  PMID: 8943725

Abstract

Intraepithelial T lymphocytes in the small intestine (IEL) consist of alpha beta T-cell receptor (TCR)-bearing T cells (alpha beta-IEL) and gamma delta TCR-bearing T cells (gamma delta-IEL). Development and cytolytic activation of alpha beta-IEL sharply attenuate in germ-free (GF) mice fed a natural diet (Nat-GF), but the number and cytotoxicity of gamma delta-IEL are comparable between conventional (CV) and Nat-GF mice. In this report, we compared the properties of IEL in Nat-GF mice and GF mice fed antigen-minimized diet (AgM-GF mice) of C57BL/6 strain to evaluate an influence of gut antigenic load on IEL development. Numbers of alpha beta-IEL and gamma delta-IEL in AgM-GF mice were less by 1.9- and 1.4-fold than those in Nat-GF mice, respectively. Significant decreases in the proportions of CD4+8-, CD4-8 alpha beta +, and CD4+8+ subsets and a resultant increase in the ratio of CD4-8 alpha alpha + subset were evident in alpha beta-IEL of Nat-GF mice compared with CV mice, but the subset constitution of alpha beta-IEL was similar between Nat-GF and AgM-GF mice. In contrast, relative composition of gamma delta-IEL was not different between CV, Nat-GF, and AgM-GF mice. alpha beta-IEL displayed low cytolytic activity in Nat-GF mice and were almost deprived of their cytotoxicity under the antigen-minimized condition. While gamma delta-IEL were strongly cytolytic in Nat-GF mice their cytolytic activity was remarkably reduced in AgM-GF mice. These results indicate that gamma delta-IEL are activated independently of microbial colonization in the gastrointestinal tract but their activation occurs in response to the exogenous antigenic substances other than live micro-organisms.

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Selected References

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  1. ABRAMS G. D., BAUER H., SPRINZ H. Influence of the normal flora on mucosal morphology and cellular renewal in the ileum. A comparison of germ-free and conventional mice. Lab Invest. 1963 Mar;12:355–364. [PubMed] [Google Scholar]
  2. Bandeira A., Itohara S., Bonneville M., Burlen-Defranoux O., Mota-Santos T., Coutinho A., Tonegawa S. Extrathymic origin of intestinal intraepithelial lymphocytes bearing T-cell antigen receptor gamma delta. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):43–47. doi: 10.1073/pnas.88.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bandeira A., Mota-Santos T., Itohara S., Degermann S., Heusser C., Tonegawa S., Coutinho A. Localization of gamma/delta T cells to the intestinal epithelium is independent of normal microbial colonization. J Exp Med. 1990 Jul 1;172(1):239–244. doi: 10.1084/jem.172.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boismenu R., Havran W. L. Modulation of epithelial cell growth by intraepithelial gamma delta T cells. Science. 1994 Nov 18;266(5188):1253–1255. doi: 10.1126/science.7973709. [DOI] [PubMed] [Google Scholar]
  5. Correa I., Bix M., Liao N. S., Zijlstra M., Jaenisch R., Raulet D. Most gamma delta T cells develop normally in beta 2-microglobulin-deficient mice. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):653–657. doi: 10.1073/pnas.89.2.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Findly R. C., Roberts S. J., Hayday A. C. Dynamic response of murine gut intraepithelial T cells after infection by the coccidian parasite Eimeria. Eur J Immunol. 1993 Oct;23(10):2557–2564. doi: 10.1002/eji.1830231027. [DOI] [PubMed] [Google Scholar]
  7. Fujiura Y., Kawaguchi M., Kondo Y., Obana S., Yamamoto H., Nanno M., Ishikawa H. Development of CD8 alpha alpha+ intestinal intraepithelial T cells in beta 2-microglobulin- and/or TAP1-deficient mice. J Immunol. 1996 Apr 15;156(8):2710–2715. [PubMed] [Google Scholar]
  8. Goodman T., Lefrancois L. Intraepithelial lymphocytes. Anatomical site, not T cell receptor form, dictates phenotype and function. J Exp Med. 1989 Nov 1;170(5):1569–1581. doi: 10.1084/jem.170.5.1569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Guy-Grand D., Cerf-Bensussan N., Malissen B., Malassis-Seris M., Briottet C., Vassalli P. Two gut intraepithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation. J Exp Med. 1991 Feb 1;173(2):471–481. doi: 10.1084/jem.173.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Guy-Grand D., Malassis-Seris M., Briottet C., Vassalli P. Cytotoxic differentiation of mouse gut thymodependent and independent intraepithelial T lymphocytes is induced locally. Correlation between functional assays, presence of perforin and granzyme transcripts, and cytoplasmic granules. J Exp Med. 1991 Jun 1;173(6):1549–1552. doi: 10.1084/jem.173.6.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hashimoto K., Handa H., Umehara K., Sasaki S. Germfree mice reared on an "antigen-free" diet. Lab Anim Sci. 1978 Feb;28(1):38–45. [PubMed] [Google Scholar]
  12. Ishikawa H., Li Y., Abeliovich A., Yamamoto S., Kaufmann S. H., Tonegawa S. Cytotoxic and interferon gamma-producing activities of gamma delta T cells in the mouse intestinal epithelium are strain dependent. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8204–8208. doi: 10.1073/pnas.90.17.8204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ito K., Van Kaer L., Bonneville M., Hsu S., Murphy D. B., Tonegawa S. Recognition of the product of a novel MHC TL region gene (27b) by a mouse gamma delta T cell receptor. Cell. 1990 Aug 10;62(3):549–561. doi: 10.1016/0092-8674(90)90019-b. [DOI] [PubMed] [Google Scholar]
  14. Kawaguchi M., Nanno M., Umesaki Y., Matsumoto S., Okada Y., Cai Z., Shimamura T., Matsuoka Y., Ohwaki M., Ishikawa H. Cytolytic activity of intestinal intraepithelial lymphocytes in germ-free mice is strain dependent and determined by T cells expressing gamma delta T-cell antigen receptors. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8591–8594. doi: 10.1073/pnas.90.18.8591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Komano H., Fujiura Y., Kawaguchi M., Matsumoto S., Hashimoto Y., Obana S., Mombaerts P., Tonegawa S., Yamamoto H., Itohara S. Homeostatic regulation of intestinal epithelia by intraepithelial gamma delta T cells. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6147–6151. doi: 10.1073/pnas.92.13.6147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lefrancois L., Goodman T. In vivo modulation of cytolytic activity and Thy-1 expression in TCR-gamma delta+ intraepithelial lymphocytes. Science. 1989 Mar 31;243(4899):1716–1718. doi: 10.1126/science.2564701. [DOI] [PubMed] [Google Scholar]
  17. London S. D., Cebra J. J., Rubin D. H. Intraepithelial lymphocytes contain virus-specific, MHC-restricted cytotoxic cell precursors after gut mucosal immunization with reovirus serotype 1/Lang. Reg Immunol. 1989 Mar-Apr;2(2):98–102. [PubMed] [Google Scholar]
  18. Matsumoto S., Setoyama H., Umesaki Y. Differential induction of major histocompatibility complex molecules on mouse intestine by bacterial colonization. Gastroenterology. 1992 Dec;103(6):1777–1782. doi: 10.1016/0016-5085(92)91434-6. [DOI] [PubMed] [Google Scholar]
  19. Penney L., Kilshaw P. J., MacDonald T. T. Regional variation in the proliferative rate and lifespan of alpha beta TCR+ and gamma delta TCR+ intraepithelial lymphocytes in the murine small intestine. Immunology. 1995 Oct;86(2):212–218. [PMC free article] [PubMed] [Google Scholar]
  20. Poussier P., Edouard P., Lee C., Binnie M., Julius M. Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes. J Exp Med. 1992 Jul 1;176(1):187–199. doi: 10.1084/jem.176.1.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Taguchi T., Aicher W. K., Fujihashi K., Yamamoto M., McGhee J. R., Bluestone J. A., Kiyono H. Novel function for intestinal intraepithelial lymphocytes. Murine CD3+, gamma/delta TCR+ T cells produce IFN-gamma and IL-5. J Immunol. 1991 Dec 1;147(11):3736–3744. [PubMed] [Google Scholar]
  22. Viney J. L., Kilshaw P. J., MacDonald T. T. Cytotoxic alpha/beta+ and gamma/delta+ T cells in murine intestinal epithelium. Eur J Immunol. 1990 Jul;20(7):1623–1626. doi: 10.1002/eji.1830200734. [DOI] [PubMed] [Google Scholar]

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