Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

MHC class II-positive epithelium and mesenchyme cells are both required for T-cell development in the thymus

Nature volume 362, pages 70–73 (1993)Cite this article

Abstract

T LYMPHOCYTES are produced in the thymus from precursors originating in the haemopoietic tissues. On entering the thymus, they undergo a programme of proliferation, T-cell receptor (TCR) gene rearrangement, differentiation and repertoire selection1. Although the thymus provides a unique environment for these events, the role of the thymic stroma in regulating specific developmental stages is not well understood2. We therefore devised an in vitro system to study the role of individual thymic stromal components in T-cell development. We report here that the development of TCR–CD4–CD8– T-cell precursors into TCR+ cells expressing CD4 and/or CDS requires the presence of both major histocom-patibility complex class II+ epithelial cells and fetal mesenchyme. The requirement for mesenchymal support can be mapped to the initial stages of intrathymic development because the later stages of maturation, from double-positive CD4+CD8+ thymocytes into single-positive CD4+ or CD8+ cells, can be supported by epithelial cells alone. We also show that the requirement for mesenchymal cells can be met by cells of the fib rob last line 3T3 (but not by supernatants from these cells). To our knowledge, these findings provide the first direct evidence that mesenchymal as well as epithelial cells are involved in T-cell development, and suggest that their involvement is stage-specific and likely to be dependent on short-range or contact-mediated interactions.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Von Boehmer, H. A. Rev. Immun. 8, 531–556 (1990).

    Article  CAS  Google Scholar 

  2. Van Ewijk, W. A. Rev. Immun. 9, 591–615 (1991).

    Article  CAS  Google Scholar 

  3. Nagamine, J. et al. J. Immun. 147, 1147–1152 (1991).

    CAS  PubMed  Google Scholar 

  4. Larsson, L. et al. Int. Immun. 1, 279–293 (1991).

    CAS  Google Scholar 

  5. Jenkinson, E. J. & Owen, J. J. T. Semin. Immun. 2, 51–58 (1990).

    CAS  Google Scholar 

  6. Jenkinson, E. J., Franchi, L. L., Kingston, R. & Owen, J. J. T. Eur. J. Immun. 12, 583–587 (1982).

    Article  CAS  Google Scholar 

  7. Jenkinson, E. J., Anderson, G. & Owen, J. J. T. J. exp Med. 176, 845–853 (1992).

    Article  CAS  Google Scholar 

  8. Kingston, R., Jenkinson, E. J. & Owen, J. J. T. Eur. J. Immun. 14, 1052–1056 (1984).

    Article  CAS  Google Scholar 

  9. Auerbach, R. Devl Biol. 2, 271–284 (1960).

    Article  CAS  Google Scholar 

  10. Mizutani, S. et al. Proc. natn. Acad. Sci. U.S.A. 84, 4999–5003 (1987).

    Article  CAS  ADS  Google Scholar 

  11. Sideras, P. & Palacios, R. Eur. J. Immun. 17, 217–221 (1987).

    Article  CAS  Google Scholar 

  12. Carding, S. R., Hayday, A. C. & Bottomly, K. Immun. Today 12, 239–245 (1991).

    Article  CAS  Google Scholar 

  13. Dexter, T. M. et al. Phil. Trans. R. Soc. B327 85–98 (1990).

    CAS  Google Scholar 

  14. Shortman, K., Egerton, M. & Spangrude, G. J. & Scollay, R. Semin. Immun. 2, 3–12 (1990).

    CAS  Google Scholar 

  15. Haynes, B. F., Shimizu, K. & Eisenbarth, G. S. J. clin. Invest. 71, 9–14 (1983).

    Article  CAS  Google Scholar 

  16. van Vliet, E., Jenkinson, E. J. & Kingston, R., Owen, J. J. T. & van Ewijk, W. Eur. J. Immun. 15, 675–681 (1985).

    Article  CAS  Google Scholar 

  17. Kanariou, M. et al. Clin. exp. Immun. 78, 263–270 (1989).

    CAS  PubMed  Google Scholar 

  18. Austyn, J. M. & Gordon, S. Eur. J. Immun. 11, 805–815 (1981).

    Article  CAS  Google Scholar 

  19. Murdoch, A., Jenkinson, E. J., Johnson, G. D. & Owen, J. J. T. J. immun. Meth. 132, 45–49 (1990).

    Article  CAS  Google Scholar 

  20. Moore, N. C., Anderson, G., Smith, C., Owen, J. J. T. & Jenkinson, E. J. Eur. J. Immun. (in the press).

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, Medical School, University of Birmingham, Birmingham, B15 2TT, UK

    Graham Anderson, Eric J. Jenkinson, Nel C. Moore & John J. T. Owen

Authors
  1. Graham Anderson
    View author publications

    Search author on:PubMed Google Scholar

  2. Eric J. Jenkinson
    View author publications

    Search author on:PubMed Google Scholar

  3. Nel C. Moore
    View author publications

    Search author on:PubMed Google Scholar

  4. John J. T. Owen
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anderson, G., Jenkinson, E., Moore, N. et al. MHC class II-positive epithelium and mesenchyme cells are both required for T-cell development in the thymus. Nature 362, 70–73 (1993). https://doi.org/10.1038/362070a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/362070a0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing