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Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond

Leukemia volume 21, pages 1387–1394 (2007)Cite this article

Abstract

The success of allogeneic stem cell transplantation and solid-organ transplantation owes much to improvements in the immunosuppressive regimens that prevent graft-versus-host disease (GVHD) or suppress allograft rejection. A better understanding of the immune mechanisms underlying induction of immunological tolerance is the key to successful transplantation. Polyclonal antibodies such as antithymocyte globulins (ATG) have been used for decades. The common belief is that ATG efficacy relies on its capacity to deplete T lymphocytes. The aim of this review is to offer an overview of the recent findings that have been demonstrated in ATG's immunomodulatory activity. The polyclonal nature of ATG is reflected in its diverse effects on the immune system: (1) T-cell depletion in blood and peripheral lymphoid tissues through complement-dependent lysis and T-cell activation and apoptosis; (2) modulation of key cell surface molecules that mediate leukocyte/endothelium interactions; (3) induction of apoptosis in B-cell lineages; (4) interference with dendritic cell functional properties; and (5) induction of regulatory T and natural killer T cells. As a consequence, ATG provides multifaceted immunomodulation paving the way for future applications and suggesting that the use of ATG should be included in the immunosuppression therapeutic armamentarium to help reduce the incidence of organ rejection and GVHD.

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Acknowledgements

We thank D Blaise (Institut Paoli-Calmettes, Marseille, France) and B Gaugler (INSERM UMR 599, Marseille, France) for helpful discussions. We also thank the physicians of the Hematology and Medical Oncology Departments at the Institut Paoli-Calmettes for their important study contributions. We apologize for the colleagues whose work could not be cited for the lack of space. We also thank the ‘Association pour la Recherche sur le Cancer (ARC; ARECA Program)’, the ‘Ligue Nationale contre le Cancer’, the ‘Fondation de France’, the ‘Fondation contre la Leucémie’, the ‘Agence de Biomédecine’, the ‘Association Cent pour Sang la Vie’ and the ‘Association Laurette Fuguain’, for their generous and continuous support for our clinical and basic research work. Our group is supported by several grants from the French ministry of health as part of the ‘Programme Hospitalier de Recherche Clinique (PHRC)’.

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  1. Unité de Transplantation et de Thérapie Cellulaire (UTTC), Institut Paoli-Calmettes, Marseille, France

    M Mohty

  2. Université de la Méditerranée, and INSERM UMR 599, Marseille, France

    M Mohty

  3. Reduced Intensity Conditioning (RIC) Subcommittee of the Acute Leukemia Working Party of EBMT,

    M Mohty

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Mohty, M. Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia 21, 1387–1394 (2007). https://doi.org/10.1038/sj.leu.2404683

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