Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance

J Immunol. 2000 Nov 1;165(9):4783-6. doi: 10.4049/jimmunol.165.9.4783.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Alemtuzumab
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm / administration & dosage
  • CD40 Ligand / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Lymphocyte Depletion / methods
  • Lymphocyte Transfusion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Skin Transplantation / immunology
  • T-Lymphocytes / transplantation
  • Thymectomy
  • Transplantation Tolerance / genetics
  • Transplantation Tolerance / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm
  • CD40 Ligand
  • Alemtuzumab