Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Apr 1;171(4):1015–1026. doi: 10.1084/jem.171.4.1015

Transgenic mice demonstrate that epithelial homing of gamma/delta T cells is determined by cell lineages independent of T cell receptor specificity

PMCID: PMC2187834  PMID: 2109035

Abstract

gamma/delta T cells with different TCR repertoires are compartmentalized in different epithelia. This raises the possibility that the TCR-gamma/delta directs homing of T cells to these epithelia. Alternatively, the signals that induce TCR-gamma/delta expression in developing T cells may also induce homing properties in such cells, presumably in the form of cell surface receptors. We have examined this issue by studying the homing of gamma/delta T cells in transgenic mice constructed with specific pairs of rearranged gamma and delta genes. In such mice, most gamma/delta T cells express the transgene-encoded TCR. We find that homing to both skin and gut epithelia is a property of T cells and is not determined by the type of gamma and delta genes used to encode their TCR. We also studied the effect of TCR replacement on the expression of Thy-1 and CD8 proteins on the gamma/delta T cells associated with gut epithelia. Our results show that the expression of the appropriate type of TCR-gamma/delta is not required for the Thy-1 expression by these T cells, suggesting that Thy-1 is not an activation marker. In contrast, CD8 expression by gut gamma/delta T cells seems to depend on the expression of the appropriate type of TCR.

Full Text

The Full Text of this article is available as a PDF (907.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Asarnow D. M., Kuziel W. A., Bonyhadi M., Tigelaar R. E., Tucker P. W., Allison J. P. Limited diversity of gamma delta antigen receptor genes of Thy-1+ dendritic epidermal cells. Cell. 1988 Dec 2;55(5):837–847. doi: 10.1016/0092-8674(88)90139-0. [DOI] [PubMed] [Google Scholar]
  2. Bank I., DePinho R. A., Brenner M. B., Cassimeris J., Alt F. W., Chess L. A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes. Nature. 1986 Jul 10;322(6075):179–181. doi: 10.1038/322179a0. [DOI] [PubMed] [Google Scholar]
  3. Blackman M. A., Marrack P., Kappler J. Influence of the major histocompatibility complex on positive thymic selection of V beta 17a+ T cells. Science. 1989 Apr 14;244(4901):214–217. doi: 10.1126/science.2784868. [DOI] [PubMed] [Google Scholar]
  4. Bonneville M., Ishida I., Mombaerts P., Katsuki M., Verbeek S., Berns A., Tonegawa S. Blockage of alpha beta T-cell development by TCR gamma delta transgenes. Nature. 1989 Dec 21;342(6252):931–934. doi: 10.1038/342931a0. [DOI] [PubMed] [Google Scholar]
  5. Bonneville M., Ito K., Krecko E. G., Itohara S., Kappes D., Ishida I., Kanagawa O., Janeway C. A., Murphy D. B., Tonegawa S. Recognition of a self major histocompatibility complex TL region product by gamma delta T-cell receptors. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5928–5932. doi: 10.1073/pnas.86.15.5928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
  8. Elliott J. F., Rock E. P., Patten P. A., Davis M. M., Chien Y. H. The adult T-cell receptor delta-chain is diverse and distinct from that of fetal thymocytes. Nature. 1988 Feb 18;331(6157):627–631. doi: 10.1038/331627a0. [DOI] [PubMed] [Google Scholar]
  9. Farr A. G., Nakane P. K. Immunohistochemistry with enzyme labeled antibodies: a brief review. J Immunol Methods. 1981;47(2):129–144. doi: 10.1016/0022-1759(81)90114-9. [DOI] [PubMed] [Google Scholar]
  10. Goodman T., Lefrançois L. Expression of the gamma-delta T-cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature. 1988 Jun 30;333(6176):855–858. doi: 10.1038/333855a0. [DOI] [PubMed] [Google Scholar]
  11. Havran W. L., Allison J. P. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature. 1988 Sep 29;335(6189):443–445. doi: 10.1038/335443a0. [DOI] [PubMed] [Google Scholar]
  12. Hayday A. C., Saito H., Gillies S. D., Kranz D. M., Tanigawa G., Eisen H. N., Tonegawa S. Structure, organization, and somatic rearrangement of T cell gamma genes. Cell. 1985 Feb;40(2):259–269. doi: 10.1016/0092-8674(85)90140-0. [DOI] [PubMed] [Google Scholar]
  13. Ito K., Bonneville M., Takagaki Y., Nakanishi N., Kanagawa O., Krecko E. G., Tonegawa S. Different gamma delta T-cell receptors are expressed on thymocytes at different stages of development. Proc Natl Acad Sci U S A. 1989 Jan;86(2):631–635. doi: 10.1073/pnas.86.2.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Itohara S., Nakanishi N., Kanagawa O., Kubo R., Tonegawa S. Monoclonal antibodies specific to native murine T-cell receptor gamma delta: analysis of gamma delta T cells during thymic ontogeny and in peripheral lymphoid organs. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5094–5098. doi: 10.1073/pnas.86.13.5094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kisielow P., Blüthmann H., Staerz U. D., Steinmetz M., von Boehmer H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature. 1988 Jun 23;333(6175):742–746. doi: 10.1038/333742a0. [DOI] [PubMed] [Google Scholar]
  16. Klein J. R. Ontogeny of the Thy-1-, Lyt-2+ murine intestinal intraepithelial lymphocyte. Characterization of a unique population of thymus-independent cytotoxic effector cells in the intestinal mucosa. J Exp Med. 1986 Jul 1;164(1):309–314. doi: 10.1084/jem.164.1.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kranz D. M., Saito H., Heller M., Takagaki Y., Haas W., Eisen H. N., Tonegawa S. Limited diversity of the rearranged T-cell gamma gene. 1985 Feb 28-Mar 6Nature. 313(6005):752–755. doi: 10.1038/313752a0. [DOI] [PubMed] [Google Scholar]
  18. Kubo R. T., Born W., Kappler J. W., Marrack P., Pigeon M. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. J Immunol. 1989 Apr 15;142(8):2736–2742. [PubMed] [Google Scholar]
  19. Kuziel W. A., Takashima A., Bonyhadi M., Bergstresser P. R., Allison J. P., Tigelaar R. E., Tucker P. W. Regulation of T-cell receptor gamma-chain RNA expression in murine Thy-1+ dendritic epidermal cells. Nature. 1987 Jul 16;328(6127):263–266. doi: 10.1038/328263a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mingari M. C., Varese P., Bottino C., Melioli G., Moretta A., Moretta L. Clonal analysis of CD4-CD8- human thymocytes expressing a T cell receptor gamma/delta chain. Direct evidence for the de novo expression of CD8 surface antigen and of cytolytic activity against tumor targets. Eur J Immunol. 1988 Nov;18(11):1831–1834. doi: 10.1002/eji.1830181127. [DOI] [PubMed] [Google Scholar]
  24. Nixon-Fulton J. L., Bergstresser P. R., Tigelaar R. E. Thy-1+ epidermal cells proliferate in response to concanavalin A and interleukin 2. J Immunol. 1986 Apr 15;136(8):2776–2786. [PubMed] [Google Scholar]
  25. Petit A., Ernst P. B., Befus A. D., Clark D. A., Rosenthal K. L., Ishizaka T., Bienenstock J. Murine intestinal intraepithelial lymphocytes I. Relationship of a novel Thy-1-,Lyt-1-,Lyt-2+, granulated subpopulation to natural killer cells and mast cells. Eur J Immunol. 1985 Mar;15(3):211–215. doi: 10.1002/eji.1830150302. [DOI] [PubMed] [Google Scholar]
  26. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
  27. Stingl G., Gunter K. C., Tschachler E., Yamada H., Lechler R. I., Yokoyama W. M., Steiner G., Germain R. N., Shevach E. M. Thy-1+ dendritic epidermal cells belong to the T-cell lineage. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2430–2434. doi: 10.1073/pnas.84.8.2430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Takagaki Y., Nakanishi N., Ishida I., Kanagawa O., Tonegawa S. T cell receptor-gamma and -delta genes preferentially utilized by adult thymocytes for the surface expression. J Immunol. 1989 Mar 15;142(6):2112–2121. [PubMed] [Google Scholar]
  29. Weiss A., Newton M., Crommie D. Expression of T3 in association with a molecule distinct from the T-cell antigen receptor heterodimer. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6998–7002. doi: 10.1073/pnas.83.18.6998. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES