FK506 and anti-CD40 ligand in peripheral nerve allotransplantation

Michael J. Brenner, Susan E. Mackinnon, Susan R. Rickman, Andrés Jaramillo, Thomas H.H. Tung, Daniel A. Hunter, T. Mohanakumar

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Purpose: Immunomodulatory agents are often combined in organ transplantation to minimize toxicity and enhance therapeutic effect. We hypothesized that combining low-dose FK506 with anti-CD40 Ligand (anti-CD40L mAb) would enhance regeneration through peripheral nerve allografts while preserving immune unresponsiveness. Methods: Eighty Balb/cJ mice underwent tibial nerve grafting and were randomized to 10 groups treated with combinations of anti-CD40L mAb therapy, low-dose FK506 (0.5 mg/kg/day), high-dose FK506 (2 mg/kg/day), and high-dose cyclosporine (25 mg/kg/day). At 3 weeks, histomorphometry and cytokine secretion assays were performed. Results: Animals receiving low-dose FK506 with anti-CD40L mAb exhibited robust nerve regeneration comparable to the isograft and high-dose FK506 allograft groups. Nerve density was significantly increased in the low-dose FK506 with anti-CD40L mAb group compared to animals receiving anti-CD40L mAb alone (p < 0.05). Combining anti-CD40L mAb with high dose cyclosporine decreased nerve fiber counts, nerve density, and percent nerve (p < 0.05). Interferon-γ production was markedly elevated in untreated allografts compared to all other treatment groups (p < 0.05). Cytokine secretion was intermediate in the low-dose FK506 alone group and suppressed in all remaining groups. Conclusion: When combined with anti-CD40L mAb, low-dose FK506 enhances nerve regeneration without disrupting immune unresponsiveness.

Original languageEnglish
Pages (from-to)237-249
Number of pages13
JournalRestorative Neurology and Neuroscience
Volume23
Issue number3-4
StatePublished - 2005

Keywords

  • Anti-CD40 ligand
  • FK506
  • Immune tolerance
  • Nerve allograft
  • Nerve regeneration

Fingerprint Dive into the research topics of 'FK506 and anti-CD40 ligand in peripheral nerve allotransplantation'. Together they form a unique fingerprint.

Cite this