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Critical Reviews™ in Immunology
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ISSN Print: 1040-8401
ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v27.i2.40
pages 167-218

Progress Toward Antibody-Induced Transplantation Tolerance

Daniel J. Moore
Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania; present address: Department of Pediatrics, Vanderbilt University, Nashville, TN 37232
James I. Kim
Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania
Samsher Sonawane
Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania
Heidi Yeh
Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania
Shaoping Deng
Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania
Major Kenneth Lee IV
Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania
James F. Markmann
Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania

ABSTRACT

Transplantation tolerance remains an elusive goal. Despite multiple animal models of tolerance induction using a variety of agents and protocols, it has yet to be achieved in humans with any predictability. In this review, we examine some of the antibodies directed toward T cells that show promise in prolonging graft survival in animal models and in preliminary clinical assessment. Because these antibodies work through multiple pathways, including depletion, downregulation, receptor-ligand blockade, and direct signaling, they have also helped us tease out the various components of long-lived donor-specific tolerance. In particular, we review the role of the thymus in therapies targeted at the peripheral immune system; the importance of the thymus in tolerance induced by anti-CD45RB suggests that central tolerance mechanisms may be more important than previously appreciated.


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