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.
机构:
CHU Nantes, Hop Hotel Dieu, Serv Hematol Clin, F-44093 Nantes 01, France
Univ Nantes, Fac Med, Nantes, France
INSERM, UMR 892, Nantes, FranceCHU Nantes, Hop Hotel Dieu, Serv Hematol Clin, F-44093 Nantes 01, France
Mohty, Mohamad
Gaugler, Beatrice
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机构:
Univ Franche Comte, INSERM, U645, F-25030 Besancon, FranceCHU Nantes, Hop Hotel Dieu, Serv Hematol Clin, F-44093 Nantes 01, France
机构:
Icahn Sch Med Mt Sinai, Translat Transplant Res Ctr, Dept Med, Div Nephrol, New York, NY 10029 USA
Icahn Sch Med Mt Sinai, Immunol Inst, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Translat Transplant Res Ctr, Dept Med, Div Nephrol, New York, NY 10029 USA
Ningoo, Mehek
Cruz-Encarnacion, Pamela
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Icahn Sch Med Mt Sinai, Translat Transplant Res Ctr, Dept Med, Div Nephrol, New York, NY 10029 USA
Icahn Sch Med Mt Sinai, Immunol Inst, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Translat Transplant Res Ctr, Dept Med, Div Nephrol, New York, NY 10029 USA
Cruz-Encarnacion, Pamela
Khilnani, Calla
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Icahn Sch Med Mt Sinai, Translat Transplant Res Ctr, Dept Med, Div Nephrol, New York, NY 10029 USA
Icahn Sch Med Mt Sinai, Immunol Inst, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Translat Transplant Res Ctr, Dept Med, Div Nephrol, New York, NY 10029 USA
Khilnani, Calla
Heeger, Peter S.
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Cedars Sinai Med Ctr, Comprehens Transplant Ctr, Los Angeles, CA USAIcahn Sch Med Mt Sinai, Translat Transplant Res Ctr, Dept Med, Div Nephrol, New York, NY 10029 USA
Heeger, Peter S.
Fribourg, Miguel
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Icahn Sch Med Mt Sinai, Translat Transplant Res Ctr, Dept Med, Div Nephrol, New York, NY 10029 USA
Icahn Sch Med Mt Sinai, Immunol Inst, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Translat Transplant Res Ctr, Dept Med, Div Nephrol, New York, NY 10029 USA