title: Heart allograft acceptance induced by anti-CD3 antibody in high-responder rats: effect on foxp3 and cytokine expression and graft infiltration.
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.
authors.affiliation: Collaborative Transplant Research Laboratory, Department of Surgery, University of Sydney and Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Vincent W T
authors.initials: VW
authors.lastname: Lam
authors.forename: Claire F
authors.initials: CF
authors.lastname: Taylor
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Laurence
authors.forename: Chuanmin
authors.initials: C
authors.lastname: Wang
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Sharland
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hodgkinson
authors.forename: Richard D M
authors.initials: RD
authors.lastname: Allen
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Hall
authors.forename: G Alex
authors.initials: GA
authors.lastname: Bishop
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D017252:CD3 Complex; D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat