Abstract
MEMBRANE receptors for blood proteases govern the clotting1 and fibrinolytic2 cascades, regulate signal transduction3,4, and control the growth of mesenchymal cells5,6. Despite their importance in the development of vascular injury7, it is unclear whether these mechanisms participate in the generation of an immune response. Here we report that targeting a factor Xa receptor, designated effector cell protease receptor-1 (EPR-1), with antisense oligonucleotide or with a monoclonal antibody (mAb 2E1)8 inhibited CD3/T-cell receptor-dependent lymphocyte proliferation. Immunosuppression was mediated by abolishing cytokine production and down-modulating membrane expression of the interleukin (IL)-2 receptor. In vivo administration of mAb 2E1 to severe-combined-immunodeficient mice injected with human peripheral blood leukocytes suppressed production of human immunoglobulin, abolished graft-versus-host disease, and protected these xenochimaeric mice from Epstein–Barr-virus-induced human lymphoproliferative disease. These observations indicate a new role for protease receptors in the regulation of the immune response, and identify a potential target for therapeutic immunosuppression in humans.
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References
Davie, E. W., Fujikawa, K. & Kisiel, W. Biochemistry 30, 10363–10370 (1991).
Patthy, L. Cell 41, 657–663 (1985).
Vu, T.-K. H., Hung, D. T., Wheaton, V. I. & Coughlin, S. R. Cell 64, 1057–1068 (1991).
Stitt, T. N. et al. Cell 80, 661–670 (1995).
Glenn, K. C. & Cunningham, D. D. Nature 278, 711–718 (1979).
Gasic, G. P., Arenas, C. P., Gasic, T. B. & Gasic, G. J. Proc. natn. Acad. Sci. U.S.A. 89, 2317–2320 (1992).
Ross, R. Nature 362, 801–809 (1993).
Altieri, D. C. J. biol. Chem. 269, 3139–3142 (1994).
Altieri, D. C. & Stamnes, S. J. Cell. Immun. 155, 372–383 (1994).
Rothman, B. L. et al. J. Immun. 147, 2493–2499 (1991).
Merkenschlager, M., Buck, D., Beverley, P. C. & Sattentau, Q. J. Immun. 145, 2839–2845 (1990).
Walker, C., Bettens, F. & Pichler, W. J. Eur. J. Immun. 17, 873–880 (1987).
Mosier, D. E., Gulizia, R. J., Baird, S. M. & Wilson, D. B. Nature 335, 256–259 (1988).
Mosier, D. E., Gulizia, R. J., Baird, S. M. & Wilson, D. B. Nature 338, 211 (1989).
Mosier, D. E., Gulizia, R. J., Torbett, B. E., Baird, S. M. & Wilson, D. B. Nature 353, 509 (1991).
Duchosal, M. A., Eming, S. A., McConahey, P. J. & Dixon, F. J. Am. J. Path. 141, 1097–1113 (1992).
Pirruccello, S. J. et al. Am. J. Path. 140, 1187–1194 (1992).
Veronese, M. L. et al. J. exp. Med. 176, 1763–1767 (1992).
Mosier, D. E. et al. Curr. Topics Microbiol. Immun. 152, 195–199 (1989).
Okano, M. et al. Am. J. Path. 137, 517–522 (1990).
Rowe, M. et al. J. exp. Med. 173, 147–158 (1991).
Picchio, G. R. et al. Cancer Res. 52, 2468–2477 (1992).
Janeway, C. A. Jr & Goldstein, P. Curr. Opin. Immun. 5, 313–323 (1993).
Jenkins, M. K. & Johnson, J. G. Curr. Opin. Immun. 5, 361–367 (1993).
Freeman, G. J. et al. Science 262, 907–909 (1993).
Shahinian, A. et al. Science 261, 609–612 (1993).
Duchosal, M. A. et al. Nature 355, 258–262 (1992).
Duchosal, M. A., McConahey, P. J., Robinson, C. A. & Dixon, F. J. J. exp. Med. 172, 985–988 (1990).
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Duchosal, M., Rothermel, A., McConahey, P. et al. In vivo immunosuppression by targeting a novel protease receptor. Nature 380, 352–356 (1996). https://doi.org/10.1038/380352a0
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DOI: https://doi.org/10.1038/380352a0
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