The Fas and Fas ligand pathways in liver allograft tolerance

The Fas and Fas ligand (Fas/FasL) pathways may play a central role in cytot oxicity or immunoregulation in liver transplantation. Here, in an attempt t o examine the role of Fas/FasL on drug-free tolerance, we measured mRNA lev els of Fas/FasL in livers by reverse transcriptase-polymerase chain reactio n (RT-PCR), and also protein levels of Fas/FasL in livers by immunohistoche mistry and in serum by dot blot assay. PVG recipients bearing DA livers sho wed serious rejection between post-operative (POD) days 7 and 14, but this rejection was naturally overcome without any immunosuppression. Fas gene an d protein products were expressed on almost every cell in livers taken from naive rats, and at any time point in both syngeneic and allogeneic orthoto pic liver transplantation (OLT) rats. In contrast, Fast mRNA in DA livers w as detectable at POD 7, peaked at POD 14, and declined at POD 63 in allogen eic OLT (DA-PVG). Although the Fast gene was detectable in isografts at POD 14, its expression was much lower than in allografts. The time course and localization of Fast expression indicated that the expression of Fast gradu ally switched from infiltrating cells to hepatocytes when the rejection was naturally overcome and tolerance was induced in this OLT model. Soluble Pa s could constitutively be detected at any lime point in the serum of the to lerogenic OLT (DA-PVG) rats and was not diminished during the rejection pha se. Soluble Fast peaked at POD 14 in allogeneic OLT, while sFasL was signif icantly lower in the serum of normal and syngeneic OLT rats. These findings suggest that the Fas and Fast pathways, including soluble forms, may contr ibute to the control of the immune response in this drug-free tolerance OLT model.