Heart allograft acceptance induced by anti-CD3 antibody in high-responder rats

effect on foxp3 and cytokine expression and graft infiltration

Vincent W. T. Lam, Claire F. Taylor, Jerome M. Laurence, Chuanmin Wang, Alexandra F. Sharland, Geoffrey W. McCaughan, Suzanne Hodgkinson, Richard D. M. Allen, Bruce M. Hall, G. Alex Bishop*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The ability of anti-T cell monoclonal antibody G4.18 and polyclonal anti-lymphocyte serum (ALS) to induce long-term graft survival was examined in a high-responder rat heart transplant model. Heterotopic heart allografts were performed from PVG rat strain donors to high-responder Lewis recipients. Immunosuppressive properties of G4.18 and ALS were investigated by immunohistochemistry and PCR analysis. Untreated graft rejection was 8.5 days while treatment with 1 ml ALS prolonged survival to 11.5 days (p = 0.01). Treatment with 7 mg/kg G4.18 on days 1 and 3 prolonged survival to > 100 days (p = 0.002 vs. control and p = 0.002 vs. ALS) but did not induce tolerance. Acceptance was associated with marked inhibition of cellular infiltration and inflammatory cytokine expression and only a brief, slight increase in Foxp3:T cell ratio in the graft and no increase in the spleen. In conclusion, G4.18 treatment led to long-term heart transplant survival associated with marked inhibition of early inflammation. Failure to develop tolerance was associated with a lack of early accumulation of Foxp3 cells in the graft or spleen.

Original languageEnglish
Pages (from-to)20-24
Number of pages5
JournalTransplant Immunology
Volume19
Issue number1
DOIs
Publication statusPublished - 1 Apr 2008
Externally publishedYes

Keywords

  • Cytokines
  • Heart transplantation
  • Immunosuppression
  • T-lymphocytes
  • Transplantation tolerance

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