TY - JOUR
T1 - Heart allograft acceptance induced by anti-CD3 antibody in high-responder rats
T2 - effect on foxp3 and cytokine expression and graft infiltration
AU - Lam, Vincent W. T.
AU - Taylor, Claire F.
AU - Laurence, Jerome M.
AU - Wang, Chuanmin
AU - Sharland, Alexandra F.
AU - McCaughan, Geoffrey W.
AU - Hodgkinson, Suzanne
AU - Allen, Richard D. M.
AU - Hall, Bruce M.
AU - Bishop, G. Alex
PY - 2008/4/1
Y1 - 2008/4/1
N2 - 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.
AB - 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.
KW - Cytokines
KW - Heart transplantation
KW - Immunosuppression
KW - T-lymphocytes
KW - Transplantation tolerance
UR - http://www.scopus.com/inward/record.url?scp=40849085099&partnerID=8YFLogxK
U2 - 10.1016/j.trim.2008.01.002
DO - 10.1016/j.trim.2008.01.002
M3 - Article
C2 - 18346633
AN - SCOPUS:40849085099
VL - 19
SP - 20
EP - 24
JO - Transplant Immunology
JF - Transplant Immunology
SN - 0966-3274
IS - 1
ER -