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Distribution of two types of lymphocytes (intraepithelial and lamina-propria-associated) in the murine small intestine

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Abstract

The intestine, which is exposed to nutrition and to food-derived antigens and microbes including viruses and bacteria, might be an important site for the immune response. Crucial structural and functional differences exist between the small and large intestine, regional differences even having been demonstrated within the small intestine. Accordingly, intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) might be heterogeneous among the different intestinal regions. The aim of this study has been to describe, as accurately as possible, the numbers and T-cell receptor (TCR) phenotypes of IELs and LPLs present in distinct regions of the murine small intestine under physiological conditions. Using an immunohistological technique to differentiate IELs from LPLs, the differential enumeration of IELs and LPLs in distinct regions of the murine small intestine, based upon their definition originally determined by their location, has been performed for the first time and has demonstrated that (1) there are more IELs than LPLs in the duodenum and jejunum, but more LPLs than IELs in the ileum, (2) in the duodenum and jejunum, TCRγδ IELs account for 70%–75% of the total CD3+ IELs, a much greater percentage than previously reported, (3) the ratio of TCRγδ to TCRαβ IELs is inverted in the ileum, with more than 75% IELs being TCRαβ-positive, (4) the lamina propria forms one functional unit throughout the small intestine in terms of the TCR subset components (TCRαβ:TCRγδ=3:1), and (5) the ileum is entirely different from other regions of the small intestine. To deepen our understanding of the functional significance of the small intestine as an immunologically competent organ, the precise distributions of IELs and LPLs, the ratio of their various subsets, and the strict distinction of IELs and LPLs, as described in this study, is indispensable.

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References

  • Beagley KW, Husband AJ (1998) Intraepithelial lymphocytes: origins, distribution, and function. Crit Rev Immunol 18:237–254

    CAS  PubMed  Google Scholar 

  • Beagley KW, Fujihashi K, Lagoo AS, Lagoo-Deenadaylan S, Black CA, Murray AM, Sharmanov AT, Yamamoto M, McGhee JR, Elson CO, et al (1995) Differences in intraepithelial lymphocyte T cell subsets isolated from murine small versus large intestine. J Immunol 154:5611–5619

    CAS  PubMed  Google Scholar 

  • Bland AP, Frost AJ, Lysons RJ (1995) Susceptibility of porcine ileal enterocytes to the cytotoxin of Serpulina hyodysenteriae and the resolution of the epithelial lesions—an electron-microscopic study. Vet Pathol 32:24–35

    CAS  PubMed  Google Scholar 

  • Bland PW, Warren LG (1986) Antigen presentation by epithelial cells of the rat small intestine. I. Kinetics, antigen-specificity and blocking by anti-Ia antisera. Immunology 58:1–7

    CAS  PubMed  Google Scholar 

  • Boll G, Rudolphi A, Spiess S, Reimann J (1995) Regional specialization of intraepithelial T-cells in the murine small and large-intestine. Scand J Immunol 41:103–113

    CAS  PubMed  Google Scholar 

  • Bonneville M, Ito K, Krecko EG, Itohara S, Kappes D, Ishida I, Kanagawa O, Janeway CA, Murphy DB, Tonegawa S (1989) Recognition of a self major histocompatibility complex TI region product by yb T-cell receptors. Proc Natl Acad Sci USA 86:5928–5932

    CAS  PubMed  Google Scholar 

  • Camerini V, Panwala C, Kronenberg M (1993) Regional specialization of the mucosal immune system. Intraepithelial lymphocytes of the large intestine have a different phenotype and function than those of the small intestine. J Immunol 151:1765–1776

    CAS  PubMed  Google Scholar 

  • Chardes T, Buzonigatel D, Lepage A, Bernard F, Bout D (1994) Toxoplasma gondii oral infection induces specific cytotoxic CD8-α/β(+) Thy-l(+) cut intraepithelial lymphocytes, lytic for parasite-infected enterocytes. J Immunol 153:4596–4603

    CAS  PubMed  Google Scholar 

  • Corpa JM, Juste RA, Marin JFG, Reyes LE, Gonzalez J, Perez V (2001) Distribution of lymphocyte subsets in the small intestine lymphoid tissue of 1-month-old lambs. Anat Histol Embryol J Vet Med [C] 30:121–127

    Google Scholar 

  • Duimstra JR, Myers LL, Collins JE, Benfield DA, Shoop DS, Bradbury WC (1991) Enterovirulence of enterotoxigenic Bacteroides fragilis in gnotobiotic pigs. Vet Pathol 28:514–518

    CAS  PubMed  Google Scholar 

  • Evans GS, Potten CS (1988) The distribution of endocrine cells along the mouse intestine: a quantitative immunocytochemical study. Virchows Arch B Cell Pathol 56:191–199

    CAS  Google Scholar 

  • Guy-Grand D, Cerf-Bensussan N, Malissen B, Malassis-Seris M, Briottet C, Vassalli P (1991) Two gut intraepithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation. J Exp Med 173:471–481

    CAS  PubMed  Google Scholar 

  • Haas W, Pereira P, Tonegawa S (1993) Gamma/delta cells. Annu Rev Immunol 11:637–685

    Article  CAS  PubMed  Google Scholar 

  • Hayday A, Theodoridis E, Ramsburg E, Shires J (2001) Intraepithelial lymphocytes: exploring the third way in immunology. Nat Immunol 2:997–1003

    Article  CAS  PubMed  Google Scholar 

  • Merger M, Viney JL, Borojevic R, Steele-Norwood D, Zhou P, Clark DA, Riddell R, Maric R, Podack ER, Croitoru K (2002) Defining the roles of perforin, Fas/Fasl−, and tumour necrosis factor ct in T cell induced mucosal damage in the mouse intestine. Gut 51:155–163

    Article  CAS  PubMed  Google Scholar 

  • Pabst R (1987) The anatomical basis for the immune function of the gut. Anat Embryol (Berl) 176:135–144

    Google Scholar 

  • Panja A, Siden E, Mayer L (1995) Synthesis and regulation of accessory proinflammatory cytokines by intestinal epithelial cells. Clin Exp Immunol 100:298–305

    CAS  PubMed  Google Scholar 

  • Pereira P, Gerber D, Huang SY, Tonegawa S (1995) Ontogenic development and tissue distribution of Vγl expressing γ/δ T-lymphocytes in normal mice. J Exp Med 182:1921–1930

    CAS  PubMed  Google Scholar 

  • Rocha B, Vassalli P, Guy-Grand D (1991) The Vβ repertoire of mouse gut homodimeric alpha CD8+ intraepithelial T cell receptor a/β+ lymphocytes reveals a major extrathymic pathway of T cell differentiation. J Exp Med 173:483–486

    CAS  PubMed  Google Scholar 

  • Smith HW (1965) Observations on the flora of the alimentary tract of animals and factors affecting its composition. J Pathol Bacteriol 89:95–122

    CAS  Google Scholar 

  • Suzuki H, Jeong KI, Okutani T, Doi K (2000a) Regional variations in the distribution of small intestinal intraepithelial lymphocytes in three inbred strains of mice. J Vet Med Sci 62:881–887

    Article  CAS  PubMed  Google Scholar 

  • Suzuki H, Jeong KI, Okutani T, Doi K (2000b) Regional variations in the number and subsets of intraepithelial lymphocytes in the mouse small intestine. Comp Med 50:39–42

    CAS  PubMed  Google Scholar 

  • Suzuki H, Jeong KI, Doi K (2001a) Regional variations in the distribution of small intestinal intraepithelial lymphocytes in alymphoplasia (aly/aly) mice and heterozygous (aly/+) mice. Immunol Invest 30:303–312

    Article  CAS  PubMed  Google Scholar 

  • Suzuki H, Jeong KI, Doi K (2001b) Regional variations in the distributions of small intestinal intraepithelial lymphocytes (IELs) in BALB/c+/+, nu/+, and nu/nu mice. Comp Med 51:127–133

    CAS  PubMed  Google Scholar 

  • Suzuki H, Jeong KI, Doi K (2002a) Age-related changes in the regional variations in the number and subsets of intraepithelial lymphocytes in mouse small intestine. Dev Comp Immunol 26:589–595

    Article  PubMed  Google Scholar 

  • Suzuki H, Jeong KI, Itoh K, Doi K (2002b) Regional variations in the distributions of small intestinal Intraepithelial lymphocytes in germ-free and specific pathogen-free mice. Exp Mol Pathol 72:230–235

    Article  CAS  PubMed  Google Scholar 

  • Sydora BC, Mixter PF, Houlden B, Hershberg R, Levy R, Comay M, Bluestone J, Kronenberg M (1993) T cell receptor γδ diversity and specificity of intestinal intraepithelial lymphocytes: analysis of IEL derived hybridomas. Cell Immunol 152:305–322

    Article  CAS  PubMed  Google Scholar 

  • TerSteege JCA, Buurman WA, Forget PP (1997) The neonatal development of intraepithelial and lamina propria lymphocytes in the murine small intestine. Dev Immunol 5:121–128

    PubMed  Google Scholar 

  • Viney JL, Macdonald TT, Kilshaw PJ (1989) T-cell receptor expression in intestinal intra-epithelial lymphocyte subpopulations of normal and athymic mice. Immunology 66:583–587

    CAS  PubMed  Google Scholar 

  • Ware JA, Svensson CK (1996) Longitudinal distribution of arylamine N-acetyltransferases in the intestine of the hamster, mouse, and rat. Evidence for multiplicity of N-acetyltransferases in the intestine. Biochem Pharmacol 52:1613–1620

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Tsunetoshi Itoh.

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This work was in part supported by a Grand-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan (07407066, 10470002, and 13670002 to T.I.)

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Tamura, A., Soga, H., Yaguchi, K. et al. Distribution of two types of lymphocytes (intraepithelial and lamina-propria-associated) in the murine small intestine. Cell Tissue Res 313, 47–53 (2003). https://doi.org/10.1007/s00441-003-0706-4

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