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. 1994 Oct 1;180(4):1345–1358. doi: 10.1084/jem.180.4.1345

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

PMCID: PMC2191704  PMID: 7931068

Abstract

The epithelium of the small intestine in normal euthymic mice contains a large number of intraepithelial lymphocytes (IEL), some of which bear a T cell receptor alpha/beta (TCR-alpha/beta). About half of these TCR- alpha/beta IEL display the CD8 alpha alpha phenotype and the remaining have the CD8 alpha beta or the CD4 phenotypes. To examine whether TCR- alpha/beta IEL have a TCR-beta chain repertoire as diverse as that of TCR-alpha/beta lymph node lymphocytes (LNL), we used a recently described PCR technique that allows a global analysis of the TCR-beta chain repertoire. Within any given mouse, the repertoires expressed in both CD8 alpha alpha and CD8 alpha beta TCR-alpha/beta IEL populations are oligoclonal and nonoverlapping between the two subsets. The clones are largely conserved through the length of the small intestine of the same individual. However, genetically identical individuals raised under indistinguishable environmental conditions display distinct oligoclonal repertoires. Those findings indicate that few cells of CD8 alpha alpha or of the CD8 alpha beta phenotype are responsible for the repopulation of the intestinal epithelium.

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Selected References

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  1. 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]
  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. 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]
  5. Bonneville M., Janeway C. A., Jr, Ito K., Haser W., Ishida I., Nakanishi N., Tonegawa S. Intestinal intraepithelial lymphocytes are a distinct set of gamma delta T cells. Nature. 1988 Dec 1;336(6198):479–481. doi: 10.1038/336479a0. [DOI] [PubMed] [Google Scholar]
  6. Candéias S., Waltzinger C., Benoist C., Mathis D. The V beta 17+ T cell repertoire: skewed J beta usage after thymic selection; dissimilar CDR3s in CD4+ versus CD8+ cells. J Exp Med. 1991 Nov 1;174(5):989–1000. doi: 10.1084/jem.174.5.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Casanova J. L., Pannetier C., Jaulin C., Kourilsky P. Optimal conditions for directly sequencing double-stranded PCR products with sequenase. Nucleic Acids Res. 1990 Jul 11;18(13):4028–4028. doi: 10.1093/nar/18.13.4028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cerf-Bensussan N., Jarry A., Brousse N., Lisowska-Grospierre B., Guy-Grand D., Griscelli C. A monoclonal antibody (HML-1) defining a novel membrane molecule present on human intestinal lymphocytes. Eur J Immunol. 1987 Sep;17(9):1279–1285. doi: 10.1002/eji.1830170910. [DOI] [PubMed] [Google Scholar]
  9. Cochet M., Pannetier C., Regnault A., Darche S., Leclerc C., Kourilsky P. Molecular detection and in vivo analysis of the specific T cell response to a protein antigen. Eur J Immunol. 1992 Oct;22(10):2639–2647. doi: 10.1002/eji.1830221025. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. De Geus B., Van den Enden M., Coolen C., Nagelkerken L., Van der Heijden P., Rozing J. Phenotype of intraepithelial lymphocytes in euthymic and athymic mice: implications for differentiation of cells bearing a CD3-associated gamma delta T cell receptor. Eur J Immunol. 1990 Feb;20(2):291–298. doi: 10.1002/eji.1830200210. [DOI] [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. Guy-Grand D., Griscelli C., Vassalli P. The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions. J Exp Med. 1978 Dec 1;148(6):1661–1677. doi: 10.1084/jem.148.6.1661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Guy-Grand D., Rocha B., Mintz P., Malassis-Seris M., Selz F., Malissen B., Vassalli P. Different use of T cell receptor transducing modules in two populations of gut intraepithelial lymphocytes are related to distinct pathways of T cell differentiation. J Exp Med. 1994 Aug 1;180(2):673–679. doi: 10.1084/jem.180.2.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Guy-Grand D., Vanden Broecke C., Briottet C., Malassis-Seris M., Selz F., Vassalli P. Different expression of the recombination activity gene RAG-1 in various populations of thymocytes, peripheral T cells and gut thymus-independent intraepithelial lymphocytes suggests two pathways of T cell receptor rearrangement. Eur J Immunol. 1992 Feb;22(2):505–510. doi: 10.1002/eji.1830220232. [DOI] [PubMed] [Google Scholar]
  16. Guy-Grand D., Vassalli P. Gut injury in mouse graft-versus-host reaction. Study of its occurrence and mechanisms. J Clin Invest. 1986 May;77(5):1584–1595. doi: 10.1172/JCI112474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Halstead T. E., Hall J. G. The homing of lymph-borne immunoblasts to the small gut of neonatal rats. Transplantation. 1972 Sep;14(3):339–346. doi: 10.1097/00007890-197209000-00009. [DOI] [PubMed] [Google Scholar]
  18. Landau N. R., Schatz D. G., Rosa M., Baltimore D. Increased frequency of N-region insertion in a murine pre-B-cell line infected with a terminal deoxynucleotidyl transferase retroviral expression vector. Mol Cell Biol. 1987 Sep;7(9):3237–3243. doi: 10.1128/mcb.7.9.3237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lin T., Matsuzaki G., Kenai H., Nakamura T., Nomoto K. Thymus influences the development of extrathymically derived intestinal intraepithelial lymphocytes. Eur J Immunol. 1993 Aug;23(8):1968–1974. doi: 10.1002/eji.1830230836. [DOI] [PubMed] [Google Scholar]
  20. Mosley R. L., Klein J. R. Peripheral engraftment of fetal intestine into athymic mice sponsors T cell development: direct evidence for thymopoietic function of murine small intestine. J Exp Med. 1992 Nov 1;176(5):1365–1373. doi: 10.1084/jem.176.5.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pannetier C., Cochet M., Darche S., Casrouge A., Zöller M., Kourilsky P. The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4319–4323. doi: 10.1073/pnas.90.9.4319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Poussier P., Teh H. S., Julius M. Thymus-independent positive and negative selection of T cells expressing a major histocompatibility complex class I restricted transgenic T cell receptor alpha/beta in the intestinal epithelium. J Exp Med. 1993 Dec 1;178(6):1947–1957. doi: 10.1084/jem.178.6.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rocha B., Vassalli P., Guy-Grand D. The V beta repertoire of mouse gut homodimeric alpha CD8+ intraepithelial T cell receptor alpha/beta + lymphocytes reveals a major extrathymic pathway of T cell differentiation. J Exp Med. 1991 Feb 1;173(2):483–486. doi: 10.1084/jem.173.2.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rocha B., Vassalli P., Guy-Grand D. Thymic and extrathymic origins of gut intraepithelial lymphocyte populations in mice. J Exp Med. 1994 Aug 1;180(2):681–686. doi: 10.1084/jem.180.2.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rocha B., von Boehmer H., Guy-Grand D. Selection of intraepithelial lymphocytes with CD8 alpha/alpha co-receptors by self-antigen in the murine gut. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5336–5340. doi: 10.1073/pnas.89.12.5336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Savage D. C. Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol. 1977;31:107–133. doi: 10.1146/annurev.mi.31.100177.000543. [DOI] [PubMed] [Google Scholar]
  28. Schleussner C., Ceredig R. Analysis of intraepithelial lymphocytes from major histocompatibility complex (MHC)-deficient mice: no evidence for a role of MHC class II antigens in the positive selection of V delta 4+ gamma delta T cells. Eur J Immunol. 1993 Jul;23(7):1615–1622. doi: 10.1002/eji.1830230733. [DOI] [PubMed] [Google Scholar]
  29. Sprent J. Fate of H2-activated T lymphocytes in syngeneic hosts. I. Fate in lymphoid tissues and intestines traced with 3H-thymidine, 125I-deoxyuridine and 51chromium. Cell Immunol. 1976 Feb;21(2):278–302. doi: 10.1016/0008-8749(76)90057-5. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Tomonari K., Fairchild S., Rosenwasser O. A. Influence of viral superantigens on V beta- and V alpha-specific positive and negative selection. Immunol Rev. 1993 Feb;131:131–168. doi: 10.1111/j.1600-065x.1993.tb01534.x. [DOI] [PubMed] [Google Scholar]
  32. Whetsell M., Mosley R. L., Whetsell L., Schaefer F. V., Miller K. S., Klein J. R. Rearrangement and junctional-site sequence analyses of T-cell receptor gamma genes in intestinal intraepithelial lymphocytes from murine athymic chimeras. Mol Cell Biol. 1991 Dec;11(12):5902–5909. doi: 10.1128/mcb.11.12.5902. [DOI] [PMC free article] [PubMed] [Google Scholar]

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