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

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