Skip to main content

Thank you for visiting 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.

A role for CD95 ligand in preventing graft rejection


TESTIS is a remarkable immune-privileged site, long known for its ability to support allogeneic and xenogeneic tissue transplants1á¤-4. Here we have investigated the molecular basis for testis immune privilege. Testis grafts derived from mice that can express functional CD95 (Fas or Apo-1) ligand5á¤-8 survived indefinitely when transplanted under the kidney capsule of allogeneic animals, whereas testis grafts derived from mutant gldmice, which express non-functional ligand8,9, were rejected. Further analysis of testis showed that CD95 ligand messenger RNA is constitutively expressed by testicular Sertoli cells, and that Sertoli cells from normal mice, but notgld mice, were accepted when transplanted into allogeneic recipients. CD95 ligand expression in the testis probably acts by inducing apoptotic cell death of CD95-expressing, recipient T cells activated in response to graft antigens. These findings indicate that CD95 ligand could be used to create immune-privileged tissue for a variety of transplant uses.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Barker, C. F. & Billingham, R. E. Adv. Immun. 25, 1–34 (1977).

    CAS  PubMed  Google Scholar 

  2. 2

    Bobzien, B., Yasunami, Y., Majercik, M., Lacy, P. E. & Davie, J. M. Diabetes 32, 213–216 (1983).

    CAS  Article  Google Scholar 

  3. 3

    Selawry, H. P. & Whittington, K. Diabetes 33, 405–406 (1984).

    CAS  Article  Google Scholar 

  4. 4

    Whitmore, W. F., Karsh, L. & Gittes, R. F. J. Urol. 134, 782–786 (1985).

    Article  Google Scholar 

  5. 5

    Nagata, S. & Golstein, P. Science 267, 1449–1456 (1995).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Rouvier, E., Luciani, M. F. & Golstein, P. J. exp. Med. 177, 195–200 (1993).

    CAS  Article  Google Scholar 

  7. 7

    Suda, T., Takahashi, T., Golstein, P. & Nagata, S. Cell 75, 1169–1178 (1993).

    CAS  Article  Google Scholar 

  8. 8

    Takahashi, T. et al. Int. Immun. 6, 1567–1574 (1994).

    CAS  Article  Google Scholar 

  9. 9

    Sobel, E. S., Kakkanaiah, V. N., Cohen, P. L. & Eisenberg, R. A. Int. Immun. 5, 1275–1278 (1993).

    CAS  Article  Google Scholar 

  10. 10

    Vignaux, F. & Golstein, P. Eur. J. Immun. 24, 923–927 (1994).

    CAS  Article  Google Scholar 

  11. 11

    Watanabe-Fukunaga, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A. & Nagata, S. Nature 356, 314–317 (1992).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Smith, C. A., Farrah, T. & Goodwin, R. G. Cell 76, 959–962 (1994).

    CAS  Article  Google Scholar 

  13. 13

    Miyawaki, T. et al. J. Immun. 149, 3753–3758 (1992).

    CAS  PubMed  Google Scholar 

  14. 14

    Owen-Schaub, L. B., Yonehara, S., Crump, W. L. & Grimm, E. A. Cell Immun. 140, 197–205 (1992).

    CAS  Article  Google Scholar 

  15. 15

    Cohen, P. L. & Eisenberg, R. A. Immun. Today 13, 427–428 (1992).

    CAS  Article  Google Scholar 

  16. 16

    Luciani, M. F. & Golstein, P. Phil. Trans. R. Soc. Lond. B 345, 303–309 (1994).

    CAS  Article  Google Scholar 

  17. 17

    Ju, S. T., Cui, H., Panka, D. J., Ettinger, R. & Marshak-Rothstein, A. Proc. natn. Acad. Sci. U.S.A. 91, 4185–4189 (1994).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Ramsdell, F. et al. Int. Immun. 6, 1545–1553 (1994).

    CAS  Article  Google Scholar 

  19. 19

    Stalder, T., Hahn, S. & Erb, P. J. Immun. 152, 1127–1133 (1994).

    CAS  PubMed  Google Scholar 

  20. 20

    Vignaux, F. et al. J. exp. Med. 181, 781–786 (1995).

    CAS  Article  Google Scholar 

  21. 21

    Strasser, A. Nature 373, 385–386 (1995).

    ADS  CAS  Article  Google Scholar 

  22. 22

    Russell, J. H., Rush, B., Weaver, C. & Wang, R. Proc. natn. Acad. Sci. U.S.A. 90, 4409–4413 (1993).

    ADS  CAS  Article  Google Scholar 

  23. 23

    Brunner, T. et al. Nature 373, 441–444 (1995).

    ADS  CAS  Article  Google Scholar 

  24. 24

    Dhein, J., Walczak, H., Baumler, C., Debatin, K. M. & Krammer, P. H. Nature 373, 438–441 (1995).

    ADS  CAS  Article  Google Scholar 

  25. 25

    Ju, S. T. et al. Nature 373, 444–448 (1995).

    ADS  CAS  Article  Google Scholar 

  26. 26

    Selawry, H. P., Whittington, K. B. & Bellgrau, D. Diabetes 38 (suppl.) 220–223 (1989).

    Article  Google Scholar 

  27. 27

    Cameron, D. F., Whittington, K., Schultz, R. E. & Selawry, H. P. Transplantation 50, 649–653 (1990).

    CAS  Article  Google Scholar 

  28. 28

    Selawry, H. P., Kolb, M., Herrod, H. G. & Lu, Z. N. Transplantation 52, 846–853 (1991).

    CAS  Article  Google Scholar 

  29. 29

    Selawry, H. P. & Cameron, D. F. Cell Transplant. 2, 123–129 (1993).

    CAS  Article  Google Scholar 

  30. 30

    Hao, L. et al. Transplantation 49, 609–614 (1990).

    CAS  Article  Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bellgrau, D., Gold, D., Selawry, H. et al. A role for CD95 ligand in preventing graft rejection. Nature 377, 630–632 (1995).

Download citation

Further reading


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.


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