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. 1996 Dec;89(4):494–501. doi: 10.1046/j.1365-2567.1996.d01-783.x

Microbial colonization influences composition and T-cell receptor V beta repertoire of intraepithelial lymphocytes in rat intestine.

L Helgeland 1, J T Vaage 1, B Rolstad 1, T Midtvedt 1, P Brandtzaeg 1
PMCID: PMC1456593  PMID: 9014812

Abstract

Studies in mice have shown that the composition of intestinal intraepithelial lymphocytes (IEL) may be markedly altered by gut microbial colonization. Such modulation was studied in a rat model by the use of germ-free and conventionalized animals from which IEL from the small intestine were isolated and analysed by flow cytometry. Conventionalization caused expansion as well as phenotypic alterations of T-cell receptor (TCR) alpha/beta + IEL in that the proportions of CD4+ and CD8 alpha beta + TCR alpha/beta + cells were increased, while the double negative (CD4- CD8-) fraction was reduced. microbial colonization also influenced the TCR V beta repertoire of CD8+ IEL in that the proportions of V beta 8.2+ and V beta 10+ cells were increased, whereas V beta 8.5+ and V beta 16+ cells were relatively decreased. Moreover, conventionalization influenced the levels of TCR cell surface expression in the same V beta subsets. Three-colour flow-cytometric analysis demonstrated that skewing of the V beta repertoire was most pronounced in the CD8 alpha alpha + subset, although the numerical increase of IEL mainly included the CD8 alpha beta + subset. In contrast to IEL, the TCR V beta repertoire in mesenteric lymph nodes was unchanged after intestinal colonization. These results confirm that TCR alpha/beta + IEL subpopulations respond dynamically to the microbial gut flora and suggest that their V beta repertoire can be shaped by luminal microbial antigens.

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Selected References

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  1. Aldrich C. J., Waltrip R., Hermel E., Attaya M., Lindahl K. F., Monaco J. J., Forman J. T cell recognition of QA-1b antigens on cells lacking a functional Tap-2 transporter. J Immunol. 1992 Dec 15;149(12):3773–3777. [PubMed] [Google Scholar]
  2. Badiner G., Goodman T. G., Lefrançois L. Selection of intestinal intraepithelial lymphocyte T cell receptors: evidence for a dynamic tissue-specific process. Int Immunol. 1993 Feb;5(2):223–226. doi: 10.1093/intimm/5.2.223. [DOI] [PubMed] [Google Scholar]
  3. Balk S. P., Ebert E. C., Blumenthal R. L., McDermott F. V., Wucherpfennig K. W., Landau S. B., Blumberg R. S. Oligoclonal expansion and CD1 recognition by human intestinal intraepithelial lymphocytes. Science. 1991 Sep 20;253(5026):1411–1415. doi: 10.1126/science.1716785. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Blumberg R. S., Yockey C. E., Gross G. G., Ebert E. C., Balk S. P. Human intestinal intraepithelial lymphocytes are derived from a limited number of T cell clones that utilize multiple V beta T cell receptor genes. J Immunol. 1993 Jun 1;150(11):5144–5153. [PubMed] [Google Scholar]
  6. Burke S., Landau S., Green R., Tseng C. C., Nattakom T., Canchis W., Yang L., Kaiserlian D., Gespach C., Balk S. Rat cluster of differentiation 1 molecule: expression on the surface of intestinal epithelial cells and hepatocytes. Gastroenterology. 1994 May;106(5):1143–1149. doi: 10.1016/0016-5085(94)90003-5. [DOI] [PubMed] [Google Scholar]
  7. Chardès T., Buzoni-Gatel D., Lepage A., Bernard F., Bout D. Toxoplasma gondii oral infection induces specific cytotoxic CD8 alpha/beta+ Thy-1+ gut intraepithelial lymphocytes, lytic for parasite-infected enterocytes. J Immunol. 1994 Nov 15;153(10):4596–4603. [PubMed] [Google Scholar]
  8. Cuff C. F., Cebra C. K., Rubin D. H., Cebra J. J. Developmental relationship between cytotoxic alpha/beta T cell receptor-positive intraepithelial lymphocytes and Peyer's patch lymphocytes. Eur J Immunol. 1993 Jun;23(6):1333–1339. doi: 10.1002/eji.1830230622. [DOI] [PubMed] [Google Scholar]
  9. Dogan A., Dunn-Walters D. K., MacDonald T. T., Spencer J. Demonstration of local clonality of mucosal T cells in human colon using DNA obtained by microdissection of immunohistochemically stained tissue sections. Eur J Immunol. 1996 Jun;26(6):1240–1245. doi: 10.1002/eji.1830260609. [DOI] [PubMed] [Google Scholar]
  10. Dunon D., Schwager J., Dangy J. P., Cooper M. D., Imhof B. A. T cell migration during development: homing is not related to TCR V beta 1 repertoire selection. EMBO J. 1994 Feb 15;13(4):808–815. doi: 10.1002/j.1460-2075.1994.tb06323.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gross G. G., Schwartz V. L., Stevens C., Ebert E. C., Blumberg R. S., Balk S. P. Distribution of dominant T cell receptor beta chains in human intestinal mucosa. J Exp Med. 1994 Oct 1;180(4):1337–1344. doi: 10.1084/jem.180.4.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Hershberg R., Eghtesady P., Sydora B., Brorson K., Cheroutre H., Modlin R., Kronenberg M. Expression of the thymus leukemia antigen in mouse intestinal epithelium. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9727–9731. doi: 10.1073/pnas.87.24.9727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huleatt J. W., Lefrançois L. Antigen-driven induction of CD11c on intestinal intraepithelial lymphocytes and CD8+ T cells in vivo. J Immunol. 1995 Jun 1;154(11):5684–5693. [PubMed] [Google Scholar]
  15. Hünig T., Wallny H. J., Hartley J. K., Lawetzky A., Tiefenthaler G. A monoclonal antibody to a constant determinant of the rat T cell antigen receptor that induces T cell activation. Differential reactivity with subsets of immature and mature T lymphocytes. J Exp Med. 1989 Jan 1;169(1):73–86. doi: 10.1084/jem.169.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jarry A., Cerf-Bensussan N., Brousse N., Selz F., Guy-Grand D. Subsets of CD3+ (T cell receptor alpha/beta or gamma/delta) and CD3- lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood. Eur J Immunol. 1990 May;20(5):1097–1103. doi: 10.1002/eji.1830200523. [DOI] [PubMed] [Google Scholar]
  17. Kampinga J., Kroese F. G., Pol G. H., Nieuwenhuis P., Haag F., Singh P. B., Roser B., Aspinall R. A monoclonal antibody to a determinant of the rat T cell antigen receptor expressed by a minor subset of T cells. Int Immunol. 1989;1(3):289–295. doi: 10.1093/intimm/1.3.289. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Kühnlein P., Park J. H., Herrmann T., Elbe A., Hünig T. Identification and characterization of rat gamma/delta T lymphocytes in peripheral lymphoid organs, small intestine, and skin with a monoclonal antibody to a constant determinant of the gamma/delta T cell receptor. J Immunol. 1994 Aug 1;153(3):979–986. [PubMed] [Google Scholar]
  20. Lefrancois L. Phenotypic complexity of intraepithelial lymphocytes of the small intestine. J Immunol. 1991 Sep 15;147(6):1746–1751. [PubMed] [Google Scholar]
  21. Nicolls M. R., Aversa G. G., Pearce N. W., Spinelli A., Berger M. F., Gurley K. E., Hall B. M. Induction of long-term specific tolerance to allografts in rats by therapy with an anti-CD3-like monoclonal antibody. Transplantation. 1993 Mar;55(3):459–468. doi: 10.1097/00007890-199303000-00001. [DOI] [PubMed] [Google Scholar]
  22. Offit P. A., Dudzik K. I. Rotavirus-specific cytotoxic T lymphocytes appear at the intestinal mucosal surface after rotavirus infection. J Virol. 1989 Aug;63(8):3507–3512. doi: 10.1128/jvi.63.8.3507-3512.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pamer E. G., Wang C. R., Flaherty L., Lindahl K. F., Bevan M. J. H-2M3 presents a Listeria monocytogenes peptide to cytotoxic T lymphocytes. Cell. 1992 Jul 24;70(2):215–223. doi: 10.1016/0092-8674(92)90097-v. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Poussier P., Julius M. Thymus independent T cell development and selection in the intestinal epithelium. Annu Rev Immunol. 1994;12:521–553. doi: 10.1146/annurev.iy.12.040194.002513. [DOI] [PubMed] [Google Scholar]
  26. Regnault A., Cumano A., Vassalli P., Guy-Grand D., Kourilsky P. Oligoclonal repertoire of the CD8 alpha alpha and the CD8 alpha beta TCR-alpha/beta murine intestinal intraepithelial T lymphocytes: evidence for the random emergence of T cells. J Exp Med. 1994 Oct 1;180(4):1345–1358. doi: 10.1084/jem.180.4.1345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rocha B., Guy-Grand D., Vassalli P. Extrathymic T cell differentiation. Curr Opin Immunol. 1995 Apr;7(2):235–242. doi: 10.1016/0952-7915(95)80008-5. [DOI] [PubMed] [Google Scholar]
  28. Sieling P. A., Chatterjee D., Porcelli S. A., Prigozy T. I., Mazzaccaro R. J., Soriano T., Bloom B. R., Brenner M. B., Kronenberg M., Brennan P. J. CD1-restricted T cell recognition of microbial lipoglycan antigens. Science. 1995 Jul 14;269(5221):227–230. doi: 10.1126/science.7542404. [DOI] [PubMed] [Google Scholar]
  29. Takagaki Y., DeCloux A., Bonneville M., Tonegawa S. Diversity of gamma delta T-cell receptors on murine intestinal intra-epithelial lymphocytes. Nature. 1989 Jun 29;339(6227):712–714. doi: 10.1038/339712a0. [DOI] [PubMed] [Google Scholar]
  30. Takimoto H., Nakamura T., Takeuchi M., Sumi Y., Tanaka T., Nomoto K., Yoshikai Y. Age-associated increase in number of CD4+CD8+ intestinal intraepithelial lymphocytes in rats. Eur J Immunol. 1992 Jan;22(1):159–164. doi: 10.1002/eji.1830220124. [DOI] [PubMed] [Google Scholar]
  31. Torres-Nagel N. E., Giegerich G., Gold D. P., Hünig T. Identification of rat Tcra-V 4 and 8 gene products by monoclonal antibodies and cDNA sequence. Immunogenetics. 1994;39(5):367–370. doi: 10.1007/BF00189236. [DOI] [PubMed] [Google Scholar]
  32. Torres-Nagel N. E., Gold D. P., Hünig T. Identification of rat Tcrb-V8.2, 8.5, and 10 gene products by monoclonal antibodies. Immunogenetics. 1993;37(4):305–308. doi: 10.1007/BF00187460. [DOI] [PubMed] [Google Scholar]
  33. Torres-Nagel N., Kraus E., Brown M. H., Tiefenthaler G., Mitnacht R., Williams A. F., Hünig T. Differential thymus dependence of rat CD8 isoform expression. Eur J Immunol. 1992 Nov;22(11):2841–2848. doi: 10.1002/eji.1830221113. [DOI] [PubMed] [Google Scholar]
  34. Umesaki Y., Setoyama H., Matsumoto S., Okada Y. Expansion of alpha beta T-cell receptor-bearing intestinal intraepithelial lymphocytes after microbial colonization in germ-free mice and its independence from thymus. Immunology. 1993 May;79(1):32–37. [PMC free article] [PubMed] [Google Scholar]
  35. Vaage J. T., Dissen E., Ager A., Roberts I., Fossum S., Rolstad B. T cell receptor-bearing cells among rat intestinal intraepithelial lymphocytes are mainly alpha/beta+ and are thymus dependent. Eur J Immunol. 1990 May;20(5):1193–1196. doi: 10.1002/eji.1830200538. [DOI] [PubMed] [Google Scholar]
  36. Van Kerckhove C., Russell G. J., Deusch K., Reich K., Bhan A. K., DerSimonian H., Brenner M. B. Oligoclonality of human intestinal intraepithelial T cells. J Exp Med. 1992 Jan 1;175(1):57–63. doi: 10.1084/jem.175.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Viney J. L., MacDonald T. T. Selective death of T cell receptor gamma/delta+ intraepithelial lymphocytes by apoptosis. Eur J Immunol. 1990 Dec;20(12):2809–2812. doi: 10.1002/eji.1830201242. [DOI] [PubMed] [Google Scholar]

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