Transfection of CD40Ig into liver prevents acute rejection in rat liver transplantation.
OBJECTIVE
To investigate the effect of CD40Ig upon acute rejection of rat liver transplants.


METHODS
Thirty-two orthotopic liver transplants were performed using Lewis to BN rats with "the two-cuff technique". The rats were randomly divided into three groups. Group A served as controls (n = 10); group B (n = 11) and group C (n = 11); Lipofectamine2000-pcDNA3.1 or Lipofectamine2000-pcDNA3.1. CD40Ig complex was injected into Lewis portal vein ex vivo before cold storage of the liver. On the fifth day after transplantation, three rats in each group were killed to study the pathological changes and TUNEL immune histochemistry performed to examine CD40Ig expression. Lymphocytes were obtained from the spleen. The mixed lymphocyte reaction (MLR) was performed to determine tolerance and sheep anti-human immunoglobulin G (IgG)-FITC-labeled T cells counted by flow cytometry. Postoperative survival times of rats in each group were recorded. The pathological changes of dead rats were observed.


RESULTS
The mean survival times of group A and B were 11.00 +/- 4.28 and 12.75 +/- 5.57 days, respectively. There were serious acute rejections in allograft liver in groups A and B. Apoptosis index was 33.67 +/- 5.69 versus 39.00 +/- 5.29. Group C mean survival time was 41.25 +/- 13.70 days (P < .01). Immune histochemistry showed CD40Ig-positive elements in the allograft liver, which revealed light acute rejection and apoptosis index was 0.27 +/- 0.21 (P < .01). The part of the allografted liver in a dead rat showed light acute rejection while the others displayed chronic rejection. Recipients were specifically tolerant to donors in the MLR assay. The IgG-FITC-labeled T cells accounted for 11.57% of all T cells in group C.


CONCLUSIONS
CD40Ig transfection inhibited T-cell costimulatory pathway, prevented acute rejection, and prolonged graft survival.
Zhu
J-Y
JY
Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, People's Republic of China.
Liu
Y-N
YN
Wang
D
D
Li
T
T
Leng
X-S
XS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D020287:In Situ Nick-End Labeling; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D011169:Portal Vein; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism*; D013534:Survival; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014162:Transfection; D014184:Transplantation, Homologous
C499839:CD40Ig protein, recombinant; D011993:Recombinant Fusion Proteins