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:

T-cell apoptosis detected in situ during positive and negative selection in the thymus

Abstract

BECAUSE of positive and negative selection to molecules of the major histocompatibility complex (MHC)1, only a small propor-tion of the massive numbers of T cells generated in the thymus are selected for export2,3. Immature thymocytes have a rapid turnover2, and it has long been assumed that most thymocytes die i/i siVw4,5, presumably from apoptosis6. This has yet to be proved, however, and conventional staining techniques have shown only minimal evidence of cell death in the normal thymus7,8. Using a method for detecting cells with DNA strand breaks, we now present direct evidence for apoptosis in the normal thymus. In sections of thymus from adult mice, apoptotic cells are scattered throughout the cortex and are engulfed locally by F4/80+ macrophages. Apoptosis in the thymic cortex is not reduced in MHC-deficient mice, which suggests that T-cell death is primarily a reflection of lack of positive selection rather than negative selection. Direct evidence for apoptosis due to negative selection was obtained by crossing a Vβ5 transgenic line9 to I–E+ and I–E- mice: I–E+ mice are known to eliminate Vβ5+ T cells in the thymus whereas I–E- mice do not10. In marked contrast to I–E- mice, the medulla of I–E+ Vβ5 transgenic mice contains dense aggregates of apoptotic cells; these cells are engulfed by a distinct population of F4/80- MAC-3+ macrophages. Negative selection of Vβ5+ cells is thus restricted to the medulla.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Robey, E. & Fowlkes, B. J. A. Rev. Immun. 12, 675–705 (1994).

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  3. Tough, D. & Sprent, J. J. exp. Med. 179, 1127–1135 (1994).

    Article  CAS  PubMed  Google Scholar 

  4. Scollary, R. & Shortman, K. in Recognition and Regulation in Cell-mediated Immunity (eds Watson, J. D. & Marbrook, J.) 3–20 (Dekker, New York, 1985).

    Google Scholar 

  5. Metcalf, D. in Ciba Symposium of the Thymus: Experimental and Clinical Studies (eds Wolstenholme, G. E. W. & Porter, P.) 242–263 (Churchill, London, 1966).

    Book  Google Scholar 

  6. Kerr, J. F. R., Wyllie, A. H. & Currie, A. R. Br. J. Cancer 26, 239–257 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Saint-Marie, G. & Peng, F. S. Rev. Can. Biol. 30, 51–78 (1970).

    Google Scholar 

  8. Kendall, M. D. Immun. Today 5, 286–287 (1984).

    Article  CAS  PubMed  Google Scholar 

  9. Fink, P. J., Swan, K., Turk, G., Moore, M. W. & Carbone, F. R. J. exp. Med. 176, 1733–1738 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Woodland, D. L., Happ, M. P., Bill, J. & Palmer, E. Science 247, 964–967 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Gavrieli, Y., Sherman, Y. & Ben-Sasson, S. A. J. Cell Biol. 119, 493–501 (1992).

    Article  CAS  PubMed  Google Scholar 

  12. MacLennan, I. C. M. A. Rev. Immun. 12, 117–139 (1994).

    Article  CAS  Google Scholar 

  13. Cardell, S. C. et al. Adv. Immun. 55, 423–440 (1994).

    Article  CAS  PubMed  Google Scholar 

  14. Savill, J., Fadok, V., Henson, P. & Haslett, C. Immun. Today 14, 131–136 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. Veis, D. J., Sorenson, C. M., Shutter, J. R. & Korsmeyer, S. J. Cell 75, 229–240 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Duijvestijn, A. M. & Hoefsmit, E. C. M. Cell Tissue Res. 218, 279–292 (1981).

    Article  CAS  PubMed  Google Scholar 

  17. Wyllie, A. H. Nature 284, 555–556 (1980).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Anderson, R. E. & Warner, N. L. Adv. Immun. 24, 215–335 (1976).

    Article  CAS  PubMed  Google Scholar 

  19. Smith, C. A., Williams, G. T., Kingston, R., Jenkinson, E. J. & Owen, J. J. T. Nature 337, 181–184 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Shi, Y. et al. J. Immun. 146, 3340–3346 (1991).

    CAS  PubMed  Google Scholar 

  21. Murphy, K. M., Heimberger, A. B. & Loh, D. Y. Science 250, 1720–1723 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Hengartner, H. et al. Nature 336, 388–390 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Pullen, A. N., Kappler, J. W. & Marrack, P. Immun. Rev. 107, 125–139 (1989).

    Article  CAS  PubMed  Google Scholar 

  24. Zijlstra, M. et al. Nature 344, 742–746 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  25. Grusby, M. J., Johnson, R. S., Papaioannou, V. E. & Glimcher, L. H. Science 20, 1417–1420 (1991).

    Article  ADS  Google Scholar 

  26. Surh, C. D. et al. J. exp. Med. 176, 495–505 (1992).

    Article  CAS  PubMed  Google Scholar 

  27. Malek, T. R., Robb, R. J. & Shevach, E. M. Proc. natn. Acad. Sci. U.S.A. 80, 5694–5698 (1983).

    Article  ADS  CAS  Google Scholar 

  28. Murphy, D. B. et al. Nature 338, 765–768 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Flotte, T. J., Springer, T. A. & Thorbecke, G. J. Am. J. Path. 111, 112–124 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Surh, C., Sprent, J. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 372, 100–103 (1994). https://doi.org/10.1038/372100a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/372100a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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