Anti-CD40 ligand monoclonal antibody induces a permissive state, but not tolerance, for murine peripheral nerve allografts.
Anti-CD40 ligand monoclonal antibody prevents the interaction between CD40 and its T-cell-based ligand, thereby resulting in selective inhibition of T cell costimulation without pan-T-cell suppression. This antibody has found application in several animal models of solid organ transplantation. This study investigated use of anti-CD40 ligand antibody to promote acceptance of nerve allografts. In Experiment 1, 40 BALB/cj mice with tibial nerve transplants were administered anti-CD40 ligand antibody, a control antibody, or no treatment. In Experiment 2, 40 BALB/cj mice underwent the same regimen as in Experiment 1, but were later challenged with a second nerve allograft 3 weeks after discontinuation of treatment. Animals treated with anti-CD40 ligand antibody in Experiment 1 exhibited improved functional recovery and greater mean fiber count, fiber density, and percent nerve fiber than animals treated with control antibody or no antibody (P < 0.05). These permissive effects on nerve regeneration were associated with immune unresponsiveness on Elispot assay. The benefit of anti-CD40 ligand therapy did not persist after withdrawal of treatment (Experiment 2). Active blockade of the CD40 costimulatory pathway with murine anti-CD40 ligand antibody therefore induces a permissive state conducive to nerve regeneration across allografts but does not establish long-term tolerance.
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Michael J
MJ
Brenner
Thomas H H
TH
Tung
Susan E
SE
Mackinnon
Terence M
TM
Myckatyn
Daniel A
DA
Hunter
Thalachallour
T
Mohanakumar
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001522:Behavior, Animal; D023201:CD40 Ligand / Q000276:immunology*; D006084:Graft Rejection / Q000473:pathology; D006652:Histological Techniques / Q000379:methods; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D020127:Recovery of Function; D013979:Tibial Nerve / Q000187:drug effects* / Q000637:transplantation*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000379:methods; D014185:Transplantation, Isogeneic / Q000379:methods; D016138:Walking / Q000502:physiology; D014855:Wallerian Degeneration / Q000473:pathology
D000911:Antibodies, Monoclonal; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma