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Immunomodulation by costimulation blockade inhibits rejection of nerve allografts

In English

Författare

  • Martin Kvist
  • Vasileios Lemplesis
  • Martin Kanje
  • Henrik Ekberg
  • Mattias Corbascio
  • Lars Dahlin

Summary, in English

The aim of this study was to investigate if costimulation blockade could be used to modulate the immune response, to prevent rejection, and to stimulate regeneration into nerve allografts. Nerve allografts from Balb/C mice, and isogenic nerve grafts (isografts) from C57/BL6 mice, were used to bridge a 7-mm gap of the sciatic nerve in C57/BL6 mice. Allograft recipients were treated with either a triple treatment with anti-lymphocyte function antigen-1 (anti-LFA), anti-CD40 ligand (anti-CD40L), and cytotoxic T-lymphocyte antigen 4 immunoglobulin (anti-CTLA4Ig) or isotype antibodies (placebo) at postoperative days 0, 2, 4, and 6 (intraperitoneal). After 5 or 9 days, the nerve grafts, together with the proximal and the distal nerve segments, were evaluated by histology and immunocytochemistry for inflammatory cells [CD4-positive (CD4+) and CD8-positive (CD8+) staining cells] and axonal outgrowth (neurofilaments). The immune response was inhibited by costimulation blockade with less extensive inflammation and a lower number of CD4+ staining cells in triple-treated allografts at 9 days. The regeneration rate was significantly faster in isografts (0.75 mm/day) compared with allografts with placebo treatment (0.39 mm/day), but not when compared with triple-treated allografts (0.49 mm/day). At 9 days, the axons were significantly longer in nerve isografts than in nerve allografts, irrespective of treatment. Hence, costimulation blockade neither increased the regeneration rate nor the outgrowth length in triple-treated allografts. We conclude that costimulation blockade inhibits the immune response in nerve allografts without deterring early axonal outgrowth.

Publiceringsår

2007

Språk

Engelska

Sidor

83-90

Publikation/Tidskrift/Serie

Journal of the Peripheral Nervous System

Volym

12

Issue

2

Dokumenttyp

Artikel i tidskrift

Förlag

Wiley-Blackwell

Ämne

  • Neurosciences

Nyckelord

  • nerve allografts
  • costimulation blockade
  • nerve
  • nerve grafts
  • regeneration
  • rejection

Status

Published

Projekt

  • Nerve regeneration - signal transduktion mechanisms, timing and alternatives to nerve grafts

Forskningsgrupp

  • Renal Research Unit
  • Hand Surgery, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1085-9489