Allograft acceptance and rejection, mediated by a liver suppressor factor, LSF-1, purified from serum of liver transplanted rats.
In certain rat strain combinations liver allografts are spontaneously accepted without immunosuppression and induce donor-specific tolerance to further skin and heart graft in the recipient. Such an effect is also transferrable using serum from orthotopically liver transplanted rats (OLT serum). In the OLT serum of one such combination, DA (RT1a) donor into PVG (RT1c) recipient, a 40 kDa protein (liver suppressor factor, LSF-1) has been identified and shown to be immunosuppressive in vitro. The aim of the present study is to investigate the immunological effect of LSF-1 and a polyclonal antibody (anti-LSF-1) against this molecule, in a rat heterotopic heart transplant (HHT) model and OLT model, respectively. Intramuscular injection of 300 micrograms of LSF-1, 1 h postoperatively, into a PVG recipient of either a DA or BN (RT1n) cardiac allograft caused significant prolongation of graft survival. Intravenous injection of polyclonal rabbit sera raised against an N-terminal peptide of LSF-1 (anti-LSF-1), within 1 h postoperatively, had variable effects on the survival of DA liver grafts in PVG recipients. In 5/6 cases injection of between 1 and 2 ml of anti-LSF-1 resulted in death of the recipient. Histological examination of the liver showed severe rejection with lymphoid cell infiltration of the portal tract and sinusoids and extensive damage to the parenchyma. All control rats survived for more than 60 days without any signs of rejection. The anti-LSF-1 polyclonal antibody prevented the injection of tolerance in the normally tolerogenic model (DA into PVG). This, together with the in vivo results, suggests a role for LSF-1 in the induction of tolerance.
Edwards-Smith
C
C
Queensland Institute of Medical Research/Department of Surgery, University of Queensland, Brisbane, Australia.
Goto
S
S
Lord
R
R
Shimizu
Y
Y
Vari
F
F
Kamada
N
N
D000818:Animals; D006084:Graft Rejection / Q000209:etiology; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D007108:Immune Tolerance / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D007518:Isoantibodies / Q000494:pharmacology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D011506:Proteins; D011817:Rabbits; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous / Q000276:immunology
D006649:Histocompatibility Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D010446:Peptide Fragments; D011506:Proteins; C038353:histocompatibility antigens RT, rat; C105479:liver suppressor factor 1