The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Immunomodulation by costimulation blockade inhibits rejection of nerve allografts

På svenska

Author

  • 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.

Publishing year

2007

Language

English

Pages

83-90

Publication/Series

Journal of the Peripheral Nervous System

Volume

12

Issue

2

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Neurosciences

Keywords

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

Status

Published

Project

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

Research group

  • Renal Research Unit
  • Hand Surgery, Malmö

ISBN/ISSN/Other

  • ISSN: 1085-9489