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. 1994 Aug 1;180(2):673–679. doi: 10.1084/jem.180.2.673

Different use of T cell receptor transducing modules in two populations of gut intraepithelial lymphocytes are related to distinct pathways of T cell differentiation

PMCID: PMC2191613  PMID: 8046340

Abstract

Most gut intraepithelial cells (IEL) of the mouse are T cells that bear CD8 molecules, present either as alpha-beta chain heterodimers (CD8 beta+) or as alpha chain homodimers (CD8 beta-). All CD8 beta+ IEL bear alpha/beta T cell receptors (TCR); CD8 beta- IEL bear either alpha/beta or gamma/delta TCR and are considered to be a thymus-independent (TI) population, probably arising locally from a small fraction of CD3- IEL containing the recombinant activating gene RAG proteins. Here we report that TI CD8 beta- IEL, whether bearing alpha/beta or gamma/delta TCR, contain, in normal mice, mRNAs for both zeta and Fc epsilon RI gamma chains. These chains are present in their CD3-TCR complexes as homo- or heterodimers. In contrast, only zeta chain mRNA and homodimers are found in gut CD8 alpha/beta+ IEL and in peripheral T lymphocytes. Intestinal CD3- precursor cells contain only gamma chain, and CD3- IL- 2R+ thymocyte precursors only zeta chain mRNAs. Only very primitive thymocyte precursors contain detectable gamma chain mRNA, and it thus appears that Fc epsilon RI gamma chain use is switched off at a very early stage during thymocyte differentiation. Thus, T cell differentiation in the gut epithelium differs from that occurring in the thymus, from which CD8 beta+ IEL appear to derive. Use of different TCR transducing modules and CD8 accessory molecules between the TI and the thymus-derived T cell populations provides an explanation for their difference in reactivity to antigenic stimulations and thus in selection of repertoires.

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Selected References

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  1. Falk I., Levelt C. N., Eichmann K. Lineage relationships of the fetal thymocyte subset that expresses the beta chain of the interleukin-2 receptor. Eur J Immunol. 1993 Dec;23(12):3373–3376. doi: 10.1002/eji.1830231248. [DOI] [PubMed] [Google Scholar]
  2. Godfrey D. I., Zlotnik A. Control points in early T-cell development. Immunol Today. 1993 Nov;14(11):547–553. doi: 10.1016/0167-5699(93)90186-O. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. Guy-Grand D., Vassalli P. Gut intraepithelial T lymphocytes. Curr Opin Immunol. 1993 Apr;5(2):247–252. doi: 10.1016/0952-7915(93)90012-h. [DOI] [PubMed] [Google Scholar]
  9. Irving B. A., Chan A. C., Weiss A. Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain. J Exp Med. 1993 Apr 1;177(4):1093–1103. doi: 10.1084/jem.177.4.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lafaille J. J., DeCloux A., Bonneville M., Takagaki Y., Tonegawa S. Junctional sequences of T cell receptor gamma delta genes: implications for gamma delta T cell lineages and for a novel intermediate of V-(D)-J joining. Cell. 1989 Dec 1;59(5):859–870. doi: 10.1016/0092-8674(89)90609-0. [DOI] [PubMed] [Google Scholar]
  11. Letourneur O., Kennedy I. C., Brini A. T., Ortaldo J. R., O'Shea J. J., Kinet J. P. Characterization of the family of dimers associated with Fc receptors (Fc epsilon RI and Fc gamma RIII). J Immunol. 1991 Oct 15;147(8):2652–2656. [PubMed] [Google Scholar]
  12. Liu C. P., Ueda R., She J., Sancho J., Wang B., Weddell G., Loring J., Kurahara C., Dudley E. C., Hayday A. Abnormal T cell development in CD3-zeta-/- mutant mice and identification of a novel T cell population in the intestine. EMBO J. 1993 Dec;12(12):4863–4875. doi: 10.1002/j.1460-2075.1993.tb06176.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. López-Cabrera M., Santis A. G., Fernández-Ruiz E., Blacher R., Esch F., Sánchez-Mateos P., Sánchez-Madrid F. Molecular cloning, expression, and chromosomal localization of the human earliest lymphocyte activation antigen AIM/CD69, a new member of the C-type animal lectin superfamily of signal-transmitting receptors. J Exp Med. 1993 Aug 1;178(2):537–547. doi: 10.1084/jem.178.2.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Malissen M., Gillet A., Rocha B., Trucy J., Vivier E., Boyer C., Köntgen F., Brun N., Mazza G., Spanopoulou E. T cell development in mice lacking the CD3-zeta/eta gene. EMBO J. 1993 Nov;12(11):4347–4355. doi: 10.1002/j.1460-2075.1993.tb06119.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moingeon P., Rodewald H. R., McConkey D., Mildonian A., Awad K., Reinherz E. L. Generation of natural killer cells from both Fc gamma RII/III+ and Fc gamma RII/III- murine fetal liver progenitors. Blood. 1993 Sep 1;82(5):1453–1462. [PubMed] [Google Scholar]
  16. Mombaerts P., Clarke A. R., Rudnicki M. A., Iacomini J., Itohara S., Lafaille J. J., Wang L., Ichikawa Y., Jaenisch R., Hooper M. L. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. Nature. 1992 Nov 19;360(6401):225–231. doi: 10.1038/360225a0. [DOI] [PubMed] [Google Scholar]
  17. Mombaerts P., Iacomini J., Johnson R. S., Herrup K., Tonegawa S., Papaioannou V. E. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992 Mar 6;68(5):869–877. doi: 10.1016/0092-8674(92)90030-g. [DOI] [PubMed] [Google Scholar]
  18. Nakayama K., Nakayama K., Negishi I., Kuida K., Louie M. C., Kanagawa O., Nakauchi H., Loh D. Y. Requirement for CD8 beta chain in positive selection of CD8-lineage T cells. Science. 1994 Feb 25;263(5150):1131–1133. doi: 10.1126/science.8108731. [DOI] [PubMed] [Google Scholar]
  19. Ohno H., Aoe T., Taki S., Kitamura D., Ishida Y., Rajewsky K., Saito T. Developmental and functional impairment of T cells in mice lacking CD3 zeta chains. EMBO J. 1993 Nov;12(11):4357–4366. doi: 10.1002/j.1460-2075.1993.tb06120.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ohno H., Ono S., Hirayama N., Shimada S., Saito T. Preferential usage of the Fc receptor gamma chain in the T cell antigen receptor complex by gamma/delta T cells localized in epithelia. J Exp Med. 1994 Jan 1;179(1):365–369. doi: 10.1084/jem.179.1.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ohteki T., MacDonald H. R. Expression of the CD28 costimulatory molecule on subsets of murine intestinal intraepithelial lymphocytes correlates with lineage and responsiveness. Eur J Immunol. 1993 Jun;23(6):1251–1255. doi: 10.1002/eji.1830230609. [DOI] [PubMed] [Google Scholar]
  22. Orloff D. G., Frank S. J., Robey F. A., Weissman A. M., Klausner R. D. Biochemical characterization of the eta chain of the T-cell receptor. A unique subunit related to zeta. J Biol Chem. 1989 Sep 5;264(25):14812–14817. [PubMed] [Google Scholar]
  23. Paolini R., Kinet J. P. Cell surface control of the multiubiquitination and deubiquitination of high-affinity immunoglobulin E receptors. EMBO J. 1993 Feb;12(2):779–786. doi: 10.1002/j.1460-2075.1993.tb05712.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Qian D., Sperling A. I., Lancki D. W., Tatsumi Y., Barrett T. A., Bluestone J. A., Fitch F. W. The gamma chain of the high-affinity receptor for IgE is a major functional subunit of the T-cell antigen receptor complex in gamma delta T lymphocytes. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11875–11879. doi: 10.1073/pnas.90.24.11875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ra C., Jouvin M. H., Kinet J. P. Complete structure of the mouse mast cell receptor for IgE (Fc epsilon RI) and surface expression of chimeric receptors (rat-mouse-human) on transfected cells. J Biol Chem. 1989 Sep 15;264(26):15323–15327. [PubMed] [Google Scholar]
  26. Ravetch J. V., Kinet J. P. Fc receptors. Annu Rev Immunol. 1991;9:457–492. doi: 10.1146/annurev.iy.09.040191.002325. [DOI] [PubMed] [Google Scholar]
  27. Rocha B., Tanchot C., Von Boehmer H. Clonal anergy blocks in vivo growth of mature T cells and can be reversed in the absence of antigen. J Exp Med. 1993 May 1;177(5):1517–1521. doi: 10.1084/jem.177.5.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Rocha B., Vassalli P., Guy-Grand D. The extrathymic T-cell development pathway. Immunol Today. 1992 Nov;13(11):449–454. doi: 10.1016/0167-5699(92)90074-H. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. Rodewald H. R., Moingeon P., Lucich J. L., Dosiou C., Lopez P., Reinherz E. L. A population of early fetal thymocytes expressing Fc gamma RII/III contains precursors of T lymphocytes and natural killer cells. Cell. 1992 Apr 3;69(1):139–150. doi: 10.1016/0092-8674(92)90125-v. [DOI] [PubMed] [Google Scholar]
  33. Shinkai Y., Rathbun G., Lam K. P., Oltz E. M., Stewart V., Mendelsohn M., Charron J., Datta M., Young F., Stall A. M. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 1992 Mar 6;68(5):855–867. doi: 10.1016/0092-8674(92)90029-c. [DOI] [PubMed] [Google Scholar]
  34. Skeen M. J., Ziegler H. K. Intercellular interactions and cytokine responsiveness of peritoneal alpha/beta and gamma/delta T cells from Listeria-infected mice: synergistic effects of interleukin 1 and 7 on gamma/delta T cells. J Exp Med. 1993 Sep 1;178(3):985–996. doi: 10.1084/jem.178.3.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Takai T., Li M., Sylvestre D., Clynes R., Ravetch J. V. FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell. 1994 Feb 11;76(3):519–529. doi: 10.1016/0092-8674(94)90115-5. [DOI] [PubMed] [Google Scholar]
  36. Wegener A. M., Letourneur F., Hoeveler A., Brocker T., Luton F., Malissen B. The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules. Cell. 1992 Jan 10;68(1):83–95. doi: 10.1016/0092-8674(92)90208-t. [DOI] [PubMed] [Google Scholar]
  37. Weissman A. M., Baniyash M., Hou D., Samelson L. E., Burgess W. H., Klausner R. D. Molecular cloning of the zeta chain of the T cell antigen receptor. Science. 1988 Feb 26;239(4843):1018–1021. doi: 10.1126/science.3278377. [DOI] [PubMed] [Google Scholar]
  38. Wilson A., Held W., MacDonald H. R. Two waves of recombinase gene expression in developing thymocytes. J Exp Med. 1994 Apr 1;179(4):1355–1360. doi: 10.1084/jem.179.4.1355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ziegler S. F., Ramsdell F., Hjerrild K. A., Armitage R. J., Grabstein K. H., Hennen K. B., Farrah T., Fanslow W. C., Shevach E. M., Alderson M. R. Molecular characterization of the early activation antigen CD69: a type II membrane glycoprotein related to a family of natural killer cell activation antigens. Eur J Immunol. 1993 Jul;23(7):1643–1648. doi: 10.1002/eji.1830230737. [DOI] [PubMed] [Google Scholar]
  40. von Boehmer H. Developmental biology of T cells in T cell-receptor transgenic mice. Annu Rev Immunol. 1990;8:531–556. doi: 10.1146/annurev.iy.08.040190.002531. [DOI] [PubMed] [Google Scholar]

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