|Budget Amount *help
¥5,400,000 (Direct Cost : ¥5,400,000)
Fiscal Year 1991 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1990 : ¥3,400,000 (Direct Cost : ¥3,400,000)
The aim of this study is to investigate whether anti-class II antibody (OKIa1) can block the class II antigens of hepatic sinusoidal lining cells (SLC) using ex vivo perfusion, and whether it can prevent acute rejection in dogs not given immunosuppressants. Canine liver transplantation was performed orthotopically, either with any treatment (group 1, n=4) or with ex vivo perfusion with anti-class II antibody (group 2, n=3). SLC were separated by the collagenase and pronase digestion methods, and then mixed lymphocyte-SLC cultures (MLSLC) were performed in each group. Hepatic grafts were examined histologically and the class II expression of sinusoidal endothelial cells (SEC) and kupffer cells (KC) were compared on day 7 postoperatively. The pretransplant MLSLC in group 2 showed significant inhibition of 60 <minus-plus> 7% compared with group 1. Liver enzyme and bilirubin were significantly high in group 1 than in group 2 on day 7. In the immunohistological studies for class II expression, SLC were stained more storngly in group 1 than in group 2. The flow cytometric analysis showed that class II expression on SEC and KC in group 1 on day 7 was 71% and 63%, respectively, and while for group 2, it was 27% and 30%, respectively. Histologically, livers in group 1 showed marked evidence of acute rejection, while the livers in group 2 had no evidence of acute rejection on day
CONCLUSION : These results indicate that ex vivo perfusion of the liver with anti-class II antibody could suppress the MLSLC and class II antigen expression on SLC after transplantation, and could significantly reduce acute rejection in canine liver transplantation.
以上のごとく、本研究を通して明らかになったことは、同所性同種肝移植後の急性拒絶反応には、肝類洞壁構成細胞上に発現してくるクラスII抗原がその引き金として重要な役割を演じていること、さらに、これを抗クラスII抗体で遮断してやることによって、急性拒絶反応の制御が可能であることが示された。このような抗クラスII抗体を用いたドナー肝のex vivo perfusionは、ヒト肝移植の臨床に応用可能な人為的免疫操作法(artificial immunomodulation)といえる。