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

被引:474
|
作者
Mohty, M.
机构
[1] Inst J Paoli I Calmettes, UTTC, F-13273 Marseille 09, France
[2] Univ Mediterranee, Marseille, France
[3] INSERM, UMR 599, Marseille, France
关键词
polyclonal antibodies; T-cell depletion; regulatory T cells; dendritic cells; transplantation; immunosuppression;
D O I
10.1038/sj.leu.2404683
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1387 / 1394
页数:8
相关论文
共 50 条
  • [1] Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond
    M Mohty
    Leukemia, 2007, 21 : 1387 - 1394
  • [2] ATG MODE OF ACTION: T-CELL DEPLETION AND FAR BEYOND
    Abendroth, Dietmar K.
    Marzinzig, Michael
    KJaden, Juergen
    TRANSPLANT INTERNATIONAL, 2011, 24 : 247 - 247
  • [3] Polyclonal Rabbit Antithymocyte Globulin Exhibits Consistent Immunosuppressive Capabilities Beyond Cell Depletion
    LaCorcia, Gina
    Swistak, Mark
    Lawendowski, Carla
    Duan, Su
    Weeden, Tim
    Nahill, Sharon
    Williams, John M.
    Dzuris, John L.
    TRANSPLANTATION, 2009, 87 (07) : 966 - 974
  • [4] Partial T-cell activation and anergy induction by polyclonal antithymocyte globulin
    Merion, RM
    Howell, T
    Bromberg, JS
    TRANSPLANTATION, 1998, 65 (11) : 1481 - 1489
  • [5] Murine Antithymocyte Globulin T-Cell Depletion Is Mediated Predominantly by Macrophages, but the Fas/FasL Pathway Selectively Targets Regulatory T Cells
    Neff, Kathleen S.
    Richards, Susan M.
    Williams, John M.
    Garman, Richard D.
    Ruzek, Melanie C.
    TRANSPLANTATION, 2011, 92 (05) : 523 - 528
  • [6] Impact Of Female Donor On Allogeneic Stem Cell Transplantation Outcome Of Male Recipient After T-Cell Depletion By Rabbit Antithymocyte Globulin
    Calmettes, Claire
    Vigouroux, Stephane
    Tabrizi, Reza
    Pigneux, Arnaud
    Leguay, Thibaut
    Bouabdallah, Krimo
    Dilhuydy, Marie-Sarah
    Duclos, Cedric
    Lascaux, Axelle
    Dumas, Pierre-Yves
    Dimicoli-Salazar, Sophie
    Marit, Gerald
    Milpied, Noel
    BLOOD, 2013, 122 (21)
  • [7] IMPACT OF FEMALE DONOR ON ALLOGENEIC STEM CELL TRANSPLANTATION OUTCOME OF MALE RECIPIENT AFTER T-CELL DEPLETION BY RABBIT ANTITHYMOCYTE GLOBULIN
    Calmettes, C.
    Vigouroux, S.
    Tabrizi, R.
    Pigneux, A.
    Leguay, T.
    Bouabdallah, K.
    Dilhuydy, M. -S.
    Duclos, C.
    Lascaux, A.
    Dumas, P. -Y.
    Dimicoli-Salazar, S.
    Marit, G.
    Milpied, N.
    BONE MARROW TRANSPLANTATION, 2014, 49 : S281 - S282
  • [8] Haploidentical transplants using partial T-cell depletion, cyclosporin and low-dose antithymocyte globulin as GVHD prophylaxis.
    Russell, JA
    Chaudhry, AM
    Duggan, P
    Stewart, D
    Ruether, D
    Gluck, S
    Morris, D
    Coppes, MJ
    Anderson, R
    Wolff, J
    Egeler, M
    Booth, K
    Desai, S
    Larratt, L
    Turner, R
    Brown, CB
    BLOOD, 2000, 96 (11) : 364B - 364B
  • [9] Mechanisms of action of antithymocyte globulin: old dogs with new tricks!
    Mohty, Mohamad
    Gaugler, Beatrice
    LEUKEMIA & LYMPHOMA, 2008, 49 (09) : 1664 - 1667
  • [10] T-cell receptor sequencing reveals selected donor-reactive CD8+ T cell clones resist antithymocyte globulin depletion after kidney transplantation
    Ningoo, Mehek
    Cruz-Encarnacion, Pamela
    Khilnani, Calla
    Heeger, Peter S.
    Fribourg, Miguel
    AMERICAN JOURNAL OF TRANSPLANTATION, 2024, 24 (05) : 755 - 764