Heart allograft acceptance induced by anti-CD3 antibody in high-responder rats: effect on foxp3 and cytokine expression and graft infiltration.
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.
Lam
Vincent W T
VW
Collaborative Transplant Research Laboratory, Department of Surgery, University of Sydney and Royal Prince Alfred Hospital, Sydney, Australia.
Taylor
Claire F
CF
Laurence
Jerome M
JM
Wang
Chuanmin
C
Sharland
Alexandra F
AF
McCaughan
Geoffrey W
GW
Hodgkinson
Suzanne
S
Allen
Richard D M
RD
Hall
Bruce M
BM
Bishop
G Alex
GA
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
D000906:Antibodies; D017252:CD3 Complex; D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat