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In vivo immunosuppression by targeting a novel protease receptor

Nature volume 380, pages 352–356 (1996)Cite this article

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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Author notes

  1. Annette L. Rothermel

    Present address: The Boyer Center for Molecular Medicine, Department of Pathology, Yale University, New Haven, Connecticut, 06536, USA

Authors and Affiliations

  1. Division of Haematology, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, 1011, Switzerland

    Michel A. Duchosal

  2. The RW Johnson Pharmaceutical Research Institute, Raritan, New Jersey, USA

    Annette L. Rothermel

  3. Department of Immunology, The Scripps Research Institute, La Jolla, California, 92037, USA

    Patricia J. McConahey & Frank J. Dixon

  4. The Boyer Center for Molecular Medicine, Department of Pathology, Yale University, New Haven, Connecticut, 06536, USA

    Dario C. Altieri

Authors
  1. Michel A. Duchosal
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  2. Annette L. Rothermel
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  3. Patricia J. McConahey
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  4. Frank J. Dixon
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  5. Dario C. Altieri
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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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