New immunosuppressive proteins (KX-2, -4, and -5) induced by liver transplantation

The presence in rat serum of three novel immunosuppressive proteins is associated with induction of tolerance after liver grafting. One of these, KX-5 (40 kilodalton molecular weight) is present 40-100 days after grafting of DA liver into PVG, a combination in which liver grafts are not rejected; two others, KX-2 (87 kilodaltons) and KX-4 (10 kilodaltons), are present in PVG sera in a retransplantation model. N-terminal amino acid sequencing indicated that none of the proteins had been described previously. Induction of KX-5 was inhibited by cyclosporin A. All three proteins inhibited mixed lymphocyte responses nonspecifically. Administration of a single dose of 300 micrograms purified KX-5 to PVG rats receiving heterotopic heart allografts led to prolonged graft acceptance. The results raise the possibility of clinical application of the immunosuppressive properties of liver grafts through administration of soluble proteins.