Suppression of allogeneic response by viral XXXX gene transfer.

@entity35 @entity13358 @entity66267
Th1 cell activation and cytokine production shift the balance between Th1 and Th2, favoring the upregulation of proinflammatory activity that leads to destruction of allogeneic hepatocytes following transplantation. Th2-type cytokines. such as @entity13358 , have immune regulatory function. The aim of this study was to determine the antirejection efficacy of allogeneic hepatocytes with spheroidal shape (spheroids) genetically modified with viral @entity13358 ( @entity66267 -10). Allogeneic hepatocyte spheroids, transferred @entity66267 -10 gene by using adenovirus as the vector, were transplanted into the spleen of Nagase's analbuminemic @entity35 (NAR). NAR transplanted with @entity66267 -10-transfected hepatocytes showed an abrupt rise in serum albumin levels that peaked on day 7 and remained at high levels up to day 21 after transplantation. The peak level of albumin on day 7 in @entity66267 -10-transfected NAR was eminently higher than that in nontransfected NAR. Histopathological analysis revealed that in nontransfected NAR hepatocyte spheroids were more or less rejected on day 4, and, in contrast, @entity66267 -10-transfected spheroids were still not rejected on day 14. This protective effect correlated with sustained high @entity66267 -10 level in the splenic vein in NAR transplanted with @entity66267 -10-transfected hepatocyte spheroids, suggesting that @entity66267 -10 secreted from the transplanted hepatocytes induced an active suppression of allogeneic response. This study provides evidence to support the possibility of using @entity66267 -10 gene therapy to prevent allogeneic response in hepatocyte transplantation.
