Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1982 Jun 1;155(6):1638–1652. doi: 10.1084/jem.155.6.1638

Tolerance of thymocytes to allogeneic i region determinants encountered prethymically. Evidence for expression of anti-Ia receptors by T cell precursors before their entry into the thymus

SM Bradley, PJ Morrissey, SO Sharrow, A Singer
PMCID: PMC2186698  PMID: 6176664

Abstract

The present study has assessed whether precursor T cells express receptors specific for the recognition of allogeneic I region-encoded determinants before their entry into the thymus. Because the ability of thymocytes to proliferate in response to allogeneic stimulator cells was shown to primarily result from the recognition of allogeneic I region determinants, thymocytes must already express anti-Ia receptors. In contrast, the expression of anti- Ia receptors by functionally immature thymocyte precursors could not be directly assessed by mixed lymphocyte reaction reactivity. However, expression of anti-Ia receptors by thymocyte precursors could be assessed by their ability to be specifically tolerized by the allogeneic Ia determinants that they encountered during their differentiation. To determine whether T cell precursors could specifically recognize and be tolerized to allogeneic Ia determinants expressed prethymically, thymus- engrafted radiation bone marrow chimeras were constructed [A {arrow} A x B (Tx + A Thy)] such that strain A T cells would be differentiating within a syngeneic strain A thymus but would have been previously exposed to the allogeneic strain B Ia determinants of the irradiated A x B host. The strain A thymocytes from these experimental animals were indeed tolerant to the extrathymic allogeneic strain B Ia determinants expressed by the irradiated host. Such tolerance was not mediated by detectable suppression and was not explained by the presence intrathymically of extrathymic allogeneic Ia determinants. Thus, these results suggest that T cell precursors can be specifically tolerized entry into the thymus. In addition, the failure to detect the generation of thymocytes with specificity for the allogeneic Ia determinants of the irradiated host, which were not deleted prethymically, argues that novel anti-allo Ia receptor specificities are not generated intrathymically.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Ando I. Self-MHC-restricted cytotoxic T-cell response without thymic influence. Nature. 1981 Feb 5;289(5797):494–495. doi: 10.1038/289494a0. [DOI] [PubMed] [Google Scholar]
  2. Cytolytic thymus-derived lymphocytes specific for allogeneic stimulator cells crossreact with chemically modified syngeneic cells. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1229–1233. doi: 10.1073/pnas.74.3.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fink P. J., Bevan M. J. H-2 antigens of the thymus determine lymphocyte specificity. J Exp Med. 1978 Sep 1;148(3):766–775. doi: 10.1084/jem.148.3.766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hünig T., Bevan M. J. Self H-2 antigens influence the specificity of alloreactive cells. J Exp Med. 1980 May 1;151(5):1288–1298. doi: 10.1084/jem.151.5.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hünig T., Bevan M. J. Specificity of cytotoxic T cells from athymic mice. J Exp Med. 1980 Sep 1;152(3):688–702. doi: 10.1084/jem.152.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Janeway C. A., Wigzell H., Binz H. Two different VH gene products make up the T-cell receptors. Scand J Immunol. 1976;5(9):993–1001. doi: 10.1111/j.1365-3083.1976.tb03051.x. [DOI] [PubMed] [Google Scholar]
  7. Jerne N. K. The somatic generation of immune recognition. Eur J Immunol. 1971 Jan;1(1):1–9. doi: 10.1002/eji.1830010102. [DOI] [PubMed] [Google Scholar]
  8. Kruisbeek A. M., Sharrow S. O., Mathieson B. J., Singer A. The H-2 phenotype of the thymus dictates the self-specificity expressed by thymic but not splenic cytotoxic T lymphocyte precursors in thymus-engrafted nude mice. J Immunol. 1981 Nov;127(5):2168–2176. [PubMed] [Google Scholar]
  9. Mathieson B. J., Sharrow S. O., Bottomly K., Fowlkes B. J. Ly 9, an alloantigenic marker of lymphocyte differentiation. J Immunol. 1980 Nov;125(5):2127–2136. [PubMed] [Google Scholar]
  10. Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
  11. Sharrow S. O., Mathieson B. J., Singer A. Cell surface appearance of unexpected host MHC determinants on thymocytes from radiation bone marrow chimeras. J Immunol. 1981 Apr;126(4):1327–1335. [PubMed] [Google Scholar]
  12. Singer A., Hathcock K. S., Hodes R. J. Cellular and genetic control of antibody responses. V. Helper T-cell recognition of H-2 determinants on accessory cells but not B cells. J Exp Med. 1979 May 1;149(5):1208–1226. doi: 10.1084/jem.149.5.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Singer A., Hathcock K. S., Hodes R. J. Self recognition in allogeneic radiation bone marrow chimeras. A radiation-resistant host element dictates the self specificity and immune response gene phenotype of T-helper cells. J Exp Med. 1981 May 1;153(5):1286–1301. doi: 10.1084/jem.153.5.1286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sredni B., Schwartz R. H. Alloreactivity of an antigen-specific T-cell clone. Nature. 1980 Oct 30;287(5785):855–857. doi: 10.1038/287855a0. [DOI] [PubMed] [Google Scholar]
  15. Wagner H., Hardt C., Heeg K., Röllinghoff M., Pfizenmaier K. T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice. Nature. 1980 Mar 20;284(5753):278–278. doi: 10.1038/284278a0. [DOI] [PubMed] [Google Scholar]
  16. Wu S., Bach F. H. Helper cells in murine thymus for the generation of primary cytolytic T lymphocyte (CTL) responses in vitro. J Immunol. 1981 Feb;126(2):775–780. [PubMed] [Google Scholar]
  17. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Streilein J. W., Klein J. The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: evidence for T help. J Exp Med. 1978 Mar 1;147(3):897–911. doi: 10.1084/jem.147.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. von Boehmer H., Hengartner H., Nabholz M., Lernhardt W., Schreier M. H., Haas W. Fine specificity of a continuously growing killer cell clone specific for H-Y antigen. Eur J Immunol. 1979 Aug;9(8):592–597. doi: 10.1002/eji.1830090804. [DOI] [PubMed] [Google Scholar]

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

RESOURCES