Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Feb;86(3):1018–1022. doi: 10.1073/pnas.86.3.1018

Major histocompatibility complex class I-specific cytolytic T cells, derived from gld mice, lacking Thy-1, CD4, and CD8.

S Wadsworth 1, K Yui 1, M I Greene 1
PMCID: PMC286612  PMID: 2563589

Abstract

Thy-1 is a major cell surface molecule expressed on murine thymocytes and peripheral T cells. Its physiological function is unknown, but in vitro studies suggest that Thy-1 may transmit activation signals to T cells and may play a role in the growth and/or differentiation of thymocytes [Kroczek, R. A., Gunter, K. C., Seligmann, B. & Shevach, E. M. (1986) J. Immunol. 136, 4379-4384; Kroczek, R. A., Gunter, K. C., Germain, R. N. & Shevach, E. M. (1986) Nature (London) 322, 181-184]. However, not all mouse thymocytes are Thy-1+ [Scollay, R., Wilson, A., D'Amico, A., Kelly, K., Egerton, M., Pearse, M., Wu, L. & Shortman, K. (1988) Immunol. Rev. 104, 81-120]. In addition, C3H-gld/gld mice accumulate large numbers of Thy-1- (and Thy-1+) T-cell antigen receptor-positive CD8- CD4- (double negative) T cells in peripheral lymphoid organs. Our previous studies of these Thy-1- and Thy-1+ double negatives suggested that lack of Thy-1 expression correlated with diminished capacity to respond to T-cell stimuli. In this report, we describe a Thy-1- alpha/beta T-cell receptor-positive major histocompatibility complex-specific cytotoxic T-cell clone derived from C3H-gld/gld lymph node-residing cells. The data show that, at least in this system, Thy-1 (and CD8/CD4) expression is not required for growth, cytolytic activity, or expression of functional T-cell receptor complexes in vitro and raise the possibility that Thy-1 expression may not be obligatory in vivo for development of cytotoxic T-lymphocyte precursors in gld mice.

Full text

PDF
1019

Images in this article

1020Image
on p.1020
1021Image
on p.1021
1021Image
on p.1021
1021Image
on p.1021

Selected References

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

  1. Bier E., Hashimoto Y., Greene M. I., Maxam A. M. Active T-cell receptor genes have intron deoxyribonuclease hypersensitive sites. Science. 1985 Aug 9;229(4713):528–534. doi: 10.1126/science.3927483. [DOI] [PubMed] [Google Scholar]
  2. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  3. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
  4. Bluestone J. A., Pardoll D., Sharrow S. O., Fowlkes B. J. Characterization of murine thymocytes with CD3-associated T-cell receptor structures. Nature. 1987 Mar 5;326(6108):82–84. doi: 10.1038/326082a0. [DOI] [PubMed] [Google Scholar]
  5. Bruce J., Symington F. W., McKearn T. J., Sprent J. A monoclonal antibody discriminating between subsets of T and B cells. J Immunol. 1981 Dec;127(6):2496–2501. [PubMed] [Google Scholar]
  6. Budd R. C., Miescher G. C., Howe R. C., Lees R. K., Bron C., MacDonald H. R. Developmentally regulated expression of T cell receptor beta chain variable domains in immature thymocytes. J Exp Med. 1987 Aug 1;166(2):577–582. doi: 10.1084/jem.166.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ceredig R., Dialynas D. P., Fitch F. W., MacDonald H. R. Precursors of T cell growth factor producing cells in the thymus: ontogeny, frequency, and quantitative recovery in a subpopulation of phenotypically mature thymocytes defined by monoclonal antibody GK-1.5. J Exp Med. 1983 Nov 1;158(5):1654–1671. doi: 10.1084/jem.158.5.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davidson W. F., Dumont F. J., Bedigian H. G., Fowlkes B. J., Morse H. C., 3rd Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr/lpr and C3H-gld/gld mice. J Immunol. 1986 Jun 1;136(11):4075–4084. [PubMed] [Google Scholar]
  9. Davidson W. F., Holmes K. L., Roths J. B., Morse H. C., 3rd Immunologic abnormalities of mice bearing the gld mutation suggest a common pathway for murine nonmalignant lymphoproliferative disorders with autoimmunity. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1219–1223. doi: 10.1073/pnas.82.4.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fowlkes B. J., Kruisbeek A. M., Ton-That H., Weston M. A., Coligan J. E., Schwartz R. H., Pardoll D. M. A novel population of T-cell receptor alpha beta-bearing thymocytes which predominantly expresses a single V beta gene family. Nature. 1987 Sep 17;329(6136):251–254. doi: 10.1038/329251a0. [DOI] [PubMed] [Google Scholar]
  11. Gallatin W. M., Weissman I. L., Butcher E. C. A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature. 1983 Jul 7;304(5921):30–34. doi: 10.1038/304030a0. [DOI] [PubMed] [Google Scholar]
  12. Gunter K. C., Germain R. N., Kroczek R. A., Saito T., Yokoyama W. M., Chan C., Weiss A., Shevach E. M. Thy-1-mediated T-cell activation requires co-expression of CD3/Ti complex. Nature. 1987 Apr 2;326(6112):505–507. doi: 10.1038/326505a0. [DOI] [PubMed] [Google Scholar]
  13. Gunter K. C., Malek T. R., Shevach E. M. T cell-activating properties of an anti-Thy-1 monoclonal antibody. Possible analogy to OKT3/Leu-4. J Exp Med. 1984 Mar 1;159(3):716–730. doi: 10.1084/jem.159.3.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hashimoto Y., Yui K., Littman D., Greene M. I. T-cell receptor genes in autoimmune mice: T-cell subsets have unexpected T-cell receptor gene programs. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5883–5887. doi: 10.1073/pnas.84.16.5883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Iwamoto A., Rupp F., Ohashi P. S., Walker C. L., Pircher H., Joho R., Hengartner H., Mak T. W. T cell-specific gamma genes in C57BL/10 mice. Sequence and expression of new constant and variable region genes. J Exp Med. 1986 May 1;163(5):1203–1212. doi: 10.1084/jem.163.5.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kroczek R. A., Gunter K. C., Germain R. N., Shevach E. M. Thy-1 functions as a signal transduction molecule in T lymphocytes and transfected B lymphocytes. Nature. 1986 Jul 10;322(6075):181–184. doi: 10.1038/322181a0. [DOI] [PubMed] [Google Scholar]
  17. Kroczek R. A., Gunter K. C., Seligmann B., Shevach E. M. Induction of T cell activation by monoclonal anti-Thy-1 antibodies. J Immunol. 1986 Jun 15;136(12):4379–4384. [PubMed] [Google Scholar]
  18. Lew A. M., Pardoll D. M., Maloy W. L., Fowlkes B. J., Kruisbeek A., Cheng S. F., Germain R. N., Bluestone J. A., Schwartz R. H., Coligan J. E. Characterization of T cell receptor gamma chain expression in a subset of murine thymocytes. Science. 1986 Dec 12;234(4782):1401–1405. doi: 10.1126/science.3787252. [DOI] [PubMed] [Google Scholar]
  19. Mackay C. R., Maddox J. F., Brandon M. R. A monoclonal antibody to the p220 component of sheep LCA identifies B cells and a unique lymphocyte subset. Cell Immunol. 1987 Nov;110(1):46–55. doi: 10.1016/0008-8749(87)90100-6. [DOI] [PubMed] [Google Scholar]
  20. Moriuchi T., Chang H. C., Denome R., Silver J. Thy-1 cDNA sequence suggests a novel regulatory mechanism. Nature. 1983 Jan 6;301(5895):80–82. doi: 10.1038/301080a0. [DOI] [PubMed] [Google Scholar]
  21. Nathenson S. G., Geliebter J., Pfaffenbach G. M., Zeff R. A. Murine major histocompatibility complex class-I mutants: molecular analysis and structure-function implications. Annu Rev Immunol. 1986;4:471–502. doi: 10.1146/annurev.iy.04.040186.002351. [DOI] [PubMed] [Google Scholar]
  22. Palacios R., Kiefer M., Brockhaus M., Karjalainen K., Dembić Z., Kisielow P., von Boehmer H. Molecular, cellular, and functional properties of bone marrow T lymphocyte progenitor clones. J Exp Med. 1987 Jul 1;166(1):12–32. doi: 10.1084/jem.166.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reif A. E., Allen J. M. Mouse nervous tissue iso-antigens. Nature. 1966 Jan 29;209(5022):523–523. doi: 10.1038/209523a0. [DOI] [PubMed] [Google Scholar]
  24. Romani N., Stingl G., Tschachler E., Witmer M. D., Steinman R. M., Shevach E. M., Schuler G. The Thy-1-bearing cell of murine epidermis. A distinctive leukocyte perhaps related to natural killer cells. J Exp Med. 1985 Jun 1;161(6):1368–1383. doi: 10.1084/jem.161.6.1368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Roths J. B., Murphy E. D., Eicher E. M. A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice. J Exp Med. 1984 Jan 1;159(1):1–20. doi: 10.1084/jem.159.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature. 1984 Nov 1;312(5989):36–40. doi: 10.1038/312036a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Samelson L. E., Davidson W. F., Morse H. C., 3rd, Klausner R. D. Abnormal tyrosine phosphorylation on T-cell receptor in lymphoproliferative disorders. Nature. 1986 Dec 18;324(6098):674–676. doi: 10.1038/324674a0. [DOI] [PubMed] [Google Scholar]
  29. Scheid M. P., Landreth K. S., Tung J. S., Kincade P. W. Preferential but nonexclusive expression of macromolecular antigens on B-lineage cells. Immunol Rev. 1982;69:141–159. doi: 10.1111/j.1600-065x.1983.tb00453.x. [DOI] [PubMed] [Google Scholar]
  30. Scollay R., Wilson A., D'Amico A., Kelly K., Egerton M., Pearse M., Wu L., Shortman K. Developmental status and reconstitution potential of subpopulations of murine thymocytes. Immunol Rev. 1988 Aug;104:81–120. doi: 10.1111/j.1600-065x.1988.tb00760.x. [DOI] [PubMed] [Google Scholar]
  31. Tentori L., Pardoll D. M., Zuñiga J. C., Hu-Li J., Paul W. E., Bluestone J. A., Kruisbeek A. M. Proliferation and production of IL-2 and B cell stimulatory factor 1/IL-4 in early fetal thymocytes by activation through Thy-1 and CD3. J Immunol. 1988 Feb 15;140(4):1089–1094. [PubMed] [Google Scholar]
  32. Yui K., Hashimoto Y., Greene M. I. T cell receptors of autoimmune mice: functional and molecular analysis of novel T cell subsets in C3H-gld/gld mice. Immunol Res. 1988;7(2):173–188. doi: 10.1007/BF02918099. [DOI] [PubMed] [Google Scholar]
  33. Yui K., Wadsworth S., Yellen A., Hashimoto Y., Kokai Y., Greene M. I. Molecular and functional properties of novel T cell subsets in C3H-gld/gld and nude mice. Implications for thymic and extrathymic maturation. Immunol Rev. 1988 Aug;104:121–155. doi: 10.1111/j.1600-065x.1988.tb00761.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES