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The Journal of Immunology, 2000, 165: 4783-4786.
Copyright © 2000 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Anti-CD154 Therapeutic Antibodies Induce Infectious Transplantation Tolerance1

Luis Graca2,3, Karen Honey2, Elizabeth Adams, Stephen P. Cobbold and Herman Waldmann

Sir William Dunn School of Pathology, Oxford, United Kingdom

Nondepleting anti-CD154 (CD40 ligand) mAbs have proven effective in inducing transplantation tolerance in rodents and primates. In the induction phase, anti-CD154 Ab therapy is known to enhance apoptosis of Ag reactive T cells. However, this may not be the sole explanation for tolerance, as we show in this study that tolerance is maintained through a dominant regulatory mechanism which, like tolerance induced with CD4 Abs, manifests as infectious tolerance. Therefore, tolerance induced with anti-CD154 Abs involves not only the deletion of potentially aggressive T cells, but also a contagious spread of tolerance to new cohorts of graft-reactive T cells as they arise.




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