Abstract
Perforin-deficient mice have been generated by homologous recombination to determine whether the effects of CDS+ cytolytic T cells and natural killer cells are mediated by pore formation involving perform. These mice are viable and fertile and have normal numbers of CDS+ T cells and natural killer cells which do not lyse virus-infected or allogeneic fibroblasts or natural killer target cells in vitro. The mice fail to clear lymphocytic choriomeningitis virus and they eliminate fibrosarcoma tumour cells with reduced efficiency. Perforin is therefore a key effector molecule for T-cell- and natural killer-cell-mediated cytolysis.
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
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cerottini, J. C. & Brunner, K. T. Adv. Immun. 18, 67–132 (1974).
Lehmann-Grube, F., Moskophidis, D. & Löhler, J. Ann. N. Y. Acad. Sci. 532, 238–256 (1988).
Martz, E. & Howell, D. M. Immun. Today 10, 79–86 (1989).
Ramshaw, I., Ruby, J., Ramsay, A., Ada, G. & Karupiah, G. Immunol Rev. 127, 157–182 (1992).
Russell, J. H. Immunol. Rev. 72, 97–118 (1983).
Rouvier, E., Luciani, M. F. & Golstein, P. J. exp. Med. 177, 195–200 (1993).
Jenne, D. E. & Tschopp, J. Immunol. Rev. 103, 53–71 (1988).
Dourmashkin, R. R., Deteix, P., Simone, C. B. & Henkart, P. Clin. exp. Immun. 42, 554 (1980).
Dennert, G. & Podack, E. R. J. exp. Med. 157, 1483–1495 (1983).
Young, J. D. E., Hengartner, H., Podack, E. R. & Cohn, Z. A. Cell 44, 849–859 (1986).
Henkart, P. A. A. Rev. Immun. 3, 31–58 (1985).
Podack, E. R., Ding-E Young, J. & Cohn, Z. A. Proc. natn. Acad. Sci. U.S.A. 82, 8629–8633 (1985).
Acha-Orbea, H., Scarpellino, L., Hertig, S., Dupuis, M. & Tschopp, J. EMBO J. 9, 3815–3819 (1990).
Shiver, J. W., Su, L. & Henkart, P. A. Cell 71, 315–321 (1992).
Lichtenheld, M. et al. Nature 335, 448–451 (1988).
Shinkai, Y., Takio, K. & Okumura, K. Nature 334, 525–527 (1988).
Podack, E. R. et al. Immun. Rev. 103, 203–211 (1988).
Garcia-Sanz, J. A. et al. EMBO J. 6, 933–938 (1987).
Kawasaki, A., Shinkai, Y., Yagita, H. & Okumura, K. Eur. J. Immun. 22, 1215–1219 (1992).
Mueller, C. et al. Eur. J. Immun. 19, 1253–1259 (1989).
Mueller, C. et al. J. exp. Med. 167, 1124–1136 (1988).
Young, L. H. et al. Lancet 336, 1019–1021 (1990).
Trapani, J. A. et al. J. exp. Med. 171, 545–557 (1989).
Podack, E. R., Hengartner, H. & Lichtenheld, M. G. A. Rev. Immun. 9, 129–157 (1991).
Thomas, K. R. & Capecchi, M. R. Cell 51, 503–512 (1987).
Ledermann, B. & Bürki, K. Expl Cell Res. 197, 254–258 (1991).
Parr, E. L., Young, L. H. Y., Parr, M. B. & Young, J. D.-E. J. Immun. 145, 2365–2372 (1990).
Buchmeier, M. J., Welsh, R. M., Dutko, F. J. & Oldstone, M. B. A. Adv. Immun. 30, 275–331 (1980).
Pircher, H. P. et al. Nature 346, 629–633 (1990).
Berke, G. & Rosen, D. Transplant. Proc. 19, 412–416 (1987).
Zinkernagel, R. M. et al. J. exp. Med. 164, 1075–1092 (1986).
Moskophidis, D. & Lehmann-Grube, F. Proc. natn. Acad. Sci. U.S.A. 86, 3291–3295 (1989).
Fung-Leung, W. P., Kündig, Th. M., Zinkernagel, R. M. & Mak, T. W. J. exp. Med. 174, 1425–1429 (1991).
Muller, D. et al. Science 255, 1576–1578 (1992).
Kohler, M., Rüttner, B., Cooper, S., Hengartner, H. & Zinkernagel, R. M. Canc. Immun. Immunother. 32, 117–124 (1990).
Podack, E. R. Immun. Today 6, 21–27 (1985).
Baenziger, J., Hengartner, H., Zinkernagel, R. M. & Groscurth, P. Scand. J. Immun. 28, 411–423 (1988).
Howell, D. M. & Martz, E. J. Immun. 138, 3695–3698 (1987).
Sellins, K. S. & Cohen, J. J. J. Immun. 147, 795–803 (1991).
Huang, S. et al. Science 259, 1742–1745 (1993).
Binder, D. & Kündig, T. M. J. Immun. 146, 4301–4307 (1991).
Lehmann-Grube, F., Löhler, J., Utermöhlen, O. & Gegin, C. J. Virol. 67, 332–339 (1993).
Melief, C. J. M. Adv. Cancer Res. 58, 143–175 (1992).
Battegay, M. et al. J. Virol. Meth. 33, 191–198 (1991).
Kawasaki, A. et al. Int. Immun. 2, 678–684 (1990).
Mansour, S. L., Thomas, K. R. & Capecchi, M. R. Nature 336, 348–352 (1988).
Stewart, C. L., Schuetze, S., Vanek, M. & Wagner, E. F. EMBO J. 6, 383–388 (1987).
Youn, B. S. et al. J. exp. Med. 173, 813–822 (1991).
Cobbold, S. P., Jayasuriya, A., Nash, A., Prospero, T. D. & Waldmann, H. Nature 312, 548–551 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kägi, D., Ledermann, B., Bürki, K. et al. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 369, 31–37 (1994). https://doi.org/10.1038/369031a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/369031a0
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.