Novel immunosuppressive proteins purified from the serum of liver-retransplanted rats.
Liver grafts between certain rat strain combinations, such as DA (RT1a)-into-PVG (RT1c), are accepted without the use of immunosuppressive agents. To explore the nature and role of serum proteins in liver-induced immunosuppression, we have developed a retransplantation model of rat liver grafting. In this procedure, orthotopic liver transplantation (OLT) is carried out in the DA-into-PVG combination; two days later the DA liver is removed and a new PVG liver implanted into the same recipient (re-OLT). Serum from re-OLT rats was immunosuppressive when tested in mixed lymphocyte reactions (MLR). Three novel proteins were detected in re-OLT serum by SDS-PAGE, with sizes of 180 kD, 87 kD, and 10 kD. The N-terminal sequences of these were distinct and did not match protein sequences in the computer databases, although there was some homology between the 10 kD sequence and the beta-chain of rat hemoglobin. Purified 87 kD and 10 kD proteins were immunosuppressive in MLR; in both cases suppression was dose-dependent and nonstimulator-specific. Production of the 180 kD and 87 kD molecules required the presence of the recipient spleen. We conclude that re-OLT serum contains novel immunosuppressive proteins, which may be products of immune recognition and associated with the immediate termination of graft rejection.
Goto
S
S
Department of Surgery, University of Queensland, Herston, Brisbane, Australia.
Lord
R
R
Kobayashi
E
E
Vari
F
F
Edwards-Smith
C
C
Kamada
N
N
D000595:Amino Acid Sequence; D000818:Animals; D007166:Immunosuppressive Agents / Q000097:blood / Q000302:isolation & purification*; D016031:Liver Transplantation; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D017421:Sequence Analysis
D007166:Immunosuppressive Agents