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Immunomodulation by costimulation blockade inhibits rejection of nerve allografts

Kvist, Martin LU ; Lemplesis, Vasileios; Kanje, Martin LU ; Ekberg, Henrik LU ; Corbascio, Mattias and Dahlin, Lars LU (2007) In Journal of the Peripheral Nervous System 12(2). p.83-90
Abstract
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,... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
nerve allografts, costimulation blockade, nerve, nerve grafts, regeneration, rejection
in
Journal of the Peripheral Nervous System
volume
12
issue
2
pages
83 - 90
publisher
Wiley-Blackwell
external identifiers
  • pmid:17565532
  • wos:000247526500002
  • scopus:34250206998
ISSN
1085-9489
DOI
10.1111/j.1529-8027.2007.00126.x
language
English
LU publication?
yes
id
2fe6d143-c6fc-430d-a24a-886cc51bf3e8 (old id 650745)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17565532&dopt=Abstract
date added to LUP
2007-12-13 18:10:23
date last changed
2017-01-01 06:47:32
@article{2fe6d143-c6fc-430d-a24a-886cc51bf3e8,
  abstract     = {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.},
  author       = {Kvist, Martin and Lemplesis, Vasileios and Kanje, Martin and Ekberg, Henrik and Corbascio, Mattias and Dahlin, Lars},
  issn         = {1085-9489},
  keyword      = {nerve allografts,costimulation blockade,nerve,nerve grafts,regeneration,rejection},
  language     = {eng},
  number       = {2},
  pages        = {83--90},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of the Peripheral Nervous System},
  title        = {Immunomodulation by costimulation blockade inhibits rejection of nerve allografts},
  url          = {http://dx.doi.org/10.1111/j.1529-8027.2007.00126.x},
  volume       = {12},
  year         = {2007},
}