Analysis of immunosuppressive factors expressed in serum of liver transplanted rats

摘要

Administration of immunosuppressant is essendal for successful organ transplantation, but includes problems such as long-term medication or serious side effect. It is therefore preferable to develop a new effective immunosuppressant. In the rat model of liver transplantation, it has been known that DA livers transplanted to PVG recipients are accepted without the treatment of immunosuppressa. It has also been demonstrated that PVG recipient serum after orthotopic liver transplantation (post-OLT serum) shows in vivo immunosuppressive activity. However, the mechanism underlying such a drug-free tolerance is still unclear. Here, we characterized immunosuppressive factors expressed in post-OLT serum through evaluating immunosuppressive effect in vitro. We found that post-OLT sera possessed significant mixed lymphocyte reaction (MLR)-inhibitory activity. Since IgG level remarkably increased in post-OLT sera, we examined the role of IgG in the MLR suppression. We found that IgG depletion abrogated MLRinhibitory effect, and that purified post-OLT serum IgG suppressed MLR, suggesting that IgG antibodies are important MLR-inhibitory factor in the post-OLT serum. We next tested whether the IgG antibodies recognized specific antigen in PVG splenocytes. Western blot analysis demonstrated that three antigens (73, 34, and 31kD) were specifically recognized by post-OLT serum IgG in the early phase (7 to 21 days). Furthermore, immunodepletion of specific antibodies against these antigens abolished the MLR-inhibitory activity, suggesting that MLR-suppressive action of post-OLT IgG is mediated via recognition of these antigens.