Anti-CD40 ligand monoclonal antibody induces a permissive state, but not tolerance, for murine peripheral nerve allografts

Michael J. Brenner, Thomas H.H. Tung, Susan E. Mackinnon, Terence M. Myckatyn, Daniel A. Hunter, Thalachallour Mohanakumar

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)59-69
Number of pages11
JournalExperimental Neurology
Volume186
Issue number1
DOIs
StatePublished - Mar 2004

Keywords

  • Allograft
  • Anti-CD40 ligand
  • Elispot
  • Immune unresponsiveness
  • Monoclonal antibody
  • Mouse
  • Nerve
  • Tolerance
  • Transplantation

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