Local targeting of the CD200-CD200R axis does not promote corneal graft survival

Susan M Nicholls, David A Copland, Andrea Vitova, Lucia Kuffova, John V Forrester, Andrew D Dick

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Corneal graft rejection is primarily a CD4(+) T cell-mediated mechanism in which macrophages may play an important inflammatory role. CD200Fc fusion protein is an artificial agonist of CD200R1, a receptor expressed predominantly on myeloid cells, engagement of which is known to down-regulate macrophage function. We therefore wished to test whether CD200Fc could be used as a therapeutic agent to prolong corneal graft survival. The distribution of CD200R1 and CD200, its natural ligand, was examined by immunohistology in the cornea and conjunctiva of unoperated rats and rats that had received corneal allografts. Mouse CD200Fc was injected subconjunctivally into transplanted rats on six occasions from the day of surgery until day 10 after transplantation. Control groups received injections of mouse IgG or diluent PBS. Allo-transplants were also performed in CD200(-/-) and control mice. The ability of CD200Fc to bind rat macrophages in vitro and to inhibit nitric oxide production was tested. Mean day of rejection in CD200Fc, IgG and PBS-treated rats was 12, 10 and 9 respectively (p=0.24). Mean day of rejection in CD200(-/-) and wild type mice was 17.5 and 16.0 respectively (p=0.07). Mouse CD200Fc bound to rat macrophages in a dose-dependent manner, but was unable to inhibit nitric oxide production. The fact that treatment with CD200Fc did not inhibit graft rejection and the failure of CD200 deficiency to affect graft survival suggests that local targeting of the CD200-CD200R axis to suppress macrophage activation is not a useful therapeutic strategy in corneal graft rejection.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalExperimental Eye Research
Volume130
Early online date11 Nov 2014
DOIs
Publication statusPublished - Jan 2015

Fingerprint

Graft Survival
Graft Rejection
Macrophages
Nitric Oxide
Immunoglobulin G
Macrophage Activation
Conjunctiva
Myeloid Cells
Ambulatory Surgical Procedures
Cornea
Allografts
Therapeutics
Down-Regulation
Transplantation
Ligands
T-Lymphocytes
Transplants
Control Groups
Injections
Proteins

Keywords

  • corneal transplantation
  • graft rejection
  • CD200
  • macrophage
  • immunotherapy
  • rat
  • mouse

Cite this

Local targeting of the CD200-CD200R axis does not promote corneal graft survival. / Nicholls, Susan M; Copland, David A; Vitova, Andrea; Kuffova, Lucia; Forrester, John V; Dick, Andrew D.

In: Experimental Eye Research, Vol. 130, 01.2015, p. 1-8.

Research output: Contribution to journalArticle

Nicholls, Susan M ; Copland, David A ; Vitova, Andrea ; Kuffova, Lucia ; Forrester, John V ; Dick, Andrew D. / Local targeting of the CD200-CD200R axis does not promote corneal graft survival. In: Experimental Eye Research. 2015 ; Vol. 130. pp. 1-8.
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abstract = "Corneal graft rejection is primarily a CD4(+) T cell-mediated mechanism in which macrophages may play an important inflammatory role. CD200Fc fusion protein is an artificial agonist of CD200R1, a receptor expressed predominantly on myeloid cells, engagement of which is known to down-regulate macrophage function. We therefore wished to test whether CD200Fc could be used as a therapeutic agent to prolong corneal graft survival. The distribution of CD200R1 and CD200, its natural ligand, was examined by immunohistology in the cornea and conjunctiva of unoperated rats and rats that had received corneal allografts. Mouse CD200Fc was injected subconjunctivally into transplanted rats on six occasions from the day of surgery until day 10 after transplantation. Control groups received injections of mouse IgG or diluent PBS. Allo-transplants were also performed in CD200(-/-) and control mice. The ability of CD200Fc to bind rat macrophages in vitro and to inhibit nitric oxide production was tested. Mean day of rejection in CD200Fc, IgG and PBS-treated rats was 12, 10 and 9 respectively (p=0.24). Mean day of rejection in CD200(-/-) and wild type mice was 17.5 and 16.0 respectively (p=0.07). Mouse CD200Fc bound to rat macrophages in a dose-dependent manner, but was unable to inhibit nitric oxide production. The fact that treatment with CD200Fc did not inhibit graft rejection and the failure of CD200 deficiency to affect graft survival suggests that local targeting of the CD200-CD200R axis to suppress macrophage activation is not a useful therapeutic strategy in corneal graft rejection.",
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