Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance.
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.
Graca
L
L
Sir William Dunn School of Pathology, Oxford, United Kingdom. luis.graca@pathology.oxford.ac.uk
Honey
K
K
Adams
E
E
Cobbold
S P
SP
Waldmann
H
H
D019264:Adoptive Transfer; D000074323:Alemtuzumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D023201:CD40 Ligand / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008212:Lymphocyte Depletion / Q000379:methods; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000637:transplantation; D013934:Thymectomy; D023001:Transplantation Tolerance / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D023201:CD40 Ligand; D000074323:Alemtuzumab