The effect of combination splenectomy and low-dose FK506 therapy on graft survival after liver allograft transplantation in rats.

ABSTRACT

The effect of splenectomy on allograft survival was investigated using orthotopic liver transplantation in a rat experimental model (ACI rat liver grafted to LEW rat). Control rats without any immunosuppressive treatment died, on average, 10.4 +/- 1.4 days after operation. Splenectomy alone somewhat prolonged the survival (13.4 +/- 2.0 days), and low-dose FK506 therapy moderately prolonged it (22.7 +/- 7 days). The graft survival period was significantly prolonged (39.7 +/- 6.3 days) when them two treatments were combined. The elevation of cytotoxic antiallograft antibodies was suppressed by splenectomy but not by low-dose FK506 therapy. The development of jaundice was moderately suppressed by FK506 but not by splenectomy. There was no difference between the pattern of body weight decline in either of them two groups and that in control rats. When these two treatments were combined at the same time, the elevation of cytotoxic antibodies, development of jaundice and decline of body weight were suppressed. These data indicate that B cells play an important role in the acute rejection of the rat liver allograft at least partially via production of cytotoxic antiallograft antibody. Splenectomy or other immunosuppressive methods affecting B cells can be a supplement for immunosuppression when using reduced-dose FK506.