Thymic epithelium and the induction of transplantation tolerance in nude mice (original) (raw)

Nature volume 314, pages 454–456 (1985)Cite this article

Abstract

Immunological tolerance of self has been studied experimentally by the induction of unresponsiveness to antigens of the major histocompatibility complex (MHC) in neonatal mice1. The specific unresponsiveness resulting from such neonatal tolerance induction is first demonstrable in the thymus2,3, suggesting that neonatal tolerance is induced by some cellular component of the thymus, or at some prethymic stage. Recent transplantation studies suggest that thymic epithelium, derived by organ culturing fetal mouse thymus in the presence of deoxyguanosine, survives in an allogeneic host environment despite the continued expression of MHC donor antigens, but fails to induce allotolerance4. We demonstrate here that embryonic thymus lobes organ cultured at 24°C, a treatment that deletes the lymphohaematopoietic component of thymus leaving the epithelial matrix intact5, when transplanted to intact histoincompatible recipients, similarly survive for a prolonged period and do not induce tolerance to donor MHC antigens. However, when such culture-derived thymic epithelium is allografted to athymic nude mice, host-derived lymphocytes from both the epithelial graft and recipient spleen are unresponsive to the MHC antigens of the epithelial donor. The results suggest that, when investigated in a system which precludes the possible involvement of extrinsic mature T cells, processed by the syngeneic host thymus, thymic epithelium may induce transplantation tolerance.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Billingham, R. E., Brent, L. & Medawar, P. B. Nature 172, 603–606 (1953).
    Article ADS CAS Google Scholar
  2. Nossal, G. J. V. & Pike, B. J. Proc. natn. Acad. Sci. U.S.A. 78, 3844–3847 (1981).
    Article ADS CAS Google Scholar
  3. Wood, P. J. & Streilein, J. W. Eur. J. Immun. 12, 188–194 (1982).
    Article CAS Google Scholar
  4. Ready, A. J., Jenkinson, E. J., Kingston, R. & Owen, J. J. T. Nature 310, 231–233 (1984).
    Article ADS CAS Google Scholar
  5. Jordan, R. K. & crouse, D. A. in Development and Differentiation of Vertebrate Lymphocytes (ed. Horton, J. D.) 47–61 (Elsevier, Amsterdam, 1980).
    Google Scholar
  6. Lacy, P. E., Davie, J. M. & Finke, E. H. Science 204, 312–313 (1979).
    Article ADS CAS Google Scholar
  7. Robinson, J. H. & Jordan, R. K. Immun. Today 4, 41–45 (1983).
    Article CAS Google Scholar
  8. Jordan, R. K., Bentley, A. L., Perry, G. A. & Crouse, D. A. J. Immun. (in the press).
  9. Jordan, R. K., Robinson, J. H., Bentley, A. L., House, K. C. & Hopkinson, N. A. in Proc. 8th int. Conf. Lymphatic Tissues and Germinal Centers in Immune Reactions (ed. Klauss, G. G. B.) (Plenum, New York, in the press).
  10. Lechler, R. I. & Batchelor, J. R. J. exp. Med. 155, 31–41 (1982).
    Article CAS Google Scholar
  11. Robinson, J. H. J. Immun. 130, 1592–1595 (1983).
    CAS PubMed Google Scholar
  12. Barclay, A. N. & Mayrhofer, G. J. J. exp. Med. 153, 1660–1671 (1981).
    Article Google Scholar
  13. Fink, P. J., Bevan, M. J. & Weissman, I. L. J. exp. Med. 159, 436–451 (1984).
    Article CAS Google Scholar
  14. Dorsch, S. & Roser, B. Transplantation 33, 518–524 (1982).
    Article CAS Google Scholar
  15. Stockinger, B. Proc. natn. Acad. Sci. U.S.A. 81, 220–223 (1984).
    Article ADS CAS Google Scholar
  16. Natali, P. G., de Martino, C., Pellegrino, M. A. & Ferrone, S. Scand. J. Immun. 13, 541–546 (1981).
    Article CAS Google Scholar
  17. Jenkinson, E. J., van Ewijk, W. & Owen, J. J. T. J. exp. Med. 153, 280–292 (1981).
    Article CAS Google Scholar
  18. Bradley, S. M., Kruisbeek, A. M. & Singer, A. J. exp. Med. 156, 1650–1664 (1982).
    Article CAS Google Scholar
  19. Kast, W. M., de Waal, L. P. & Melief, J. M. J. exp. Med. 160, 1752–1766 (1984).
    Article CAS Google Scholar
  20. von Boehmer, H. & Schubiger, K. Eur. J. Immun. 14, 1048–1052 (1984).
    Article CAS Google Scholar

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK
    R. K. Jordan, J. H. Robinson, N. A. Hopkinson, K. C. House & A. L. Bentley

Authors

  1. R. K. Jordan
    You can also search for this author inPubMed Google Scholar
  2. J. H. Robinson
    You can also search for this author inPubMed Google Scholar
  3. N. A. Hopkinson
    You can also search for this author inPubMed Google Scholar
  4. K. C. House
    You can also search for this author inPubMed Google Scholar
  5. A. L. Bentley
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Jordan, R., Robinson, J., Hopkinson, N. et al. Thymic epithelium and the induction of transplantation tolerance in nude mice.Nature 314, 454–456 (1985). https://doi.org/10.1038/314454a0

Download citation