Long-term survival of cardiac allografts induced by cyclophosphamide combined with CTLA4Ig-gene transfer mediated by adenoviral vector.
There is a need to achieve donor-specific tolerance in clinical organ transplantation, where potential benefits remain overshadowed by chronic rejection and the side-effects of long-term immunosuppressive therapy. It is known that the mature immune system in mice can be reprogrammed to accept a foreign graft as if it was "self". The AdCTLA4Ig-mediated gene transfer (SC) + cyclophosphamide (CP) treatment alone prolongs allograft survival but does not induce tolerance. However, in our study, the AdCTLA4Ig-mediated gene transfer combined with SC + CP treatment yielded significantly prolonged mean survival times (149.7 +/- 18.0 days), while those in the untreated or AdLacZ treated mice were rejected in normal fashion (5.3 +/- 0.5 and 5.2 +/- 0.4 days, respectively), and survival in the AdCTLA4Ig or SC + CP treated groups were 45.7 +/- 9.6 or 50.2 +/- 5.3 days, respectively. In conclusion, a protocol of AdCTLA4Ig + SC + CP improved the survival of DA-->LEW cardiac allografts.
Wang
G M
GM
Department of Histology and Embryology, Dali University, Yunnan Province, China.
Ma
J B
JB
Jin
Y Z
YZ
Feng
Y G
YG
Hao
J
J
Gao
X
X
Xie
S S
SS
D000069594:Abatacept; D000256:Adenoviridae; D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D018796:Immunoconjugates / Q000235:genetics / Q000627:therapeutic use; D007165:Immunosuppression Therapy / Q000379:methods; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D017741:Survivors; D014184:Transplantation, Homologous / Q000276:immunology
D018796:Immunoconjugates; D000069594:Abatacept; D003520:Cyclophosphamide