title: Administration of exogenous interleukin-2 abrogates spontaneous rat liver allograft acceptance but does not affect long-term established graft survival.
abstract: BACKGROUND
  Spontaneous tolerance to the orthotopic liver allograft uniformly occurs in the DA (RT1a) to PVG (RT1c) rat combination despite a fully allogeneic barrier.
  
  
  METHODS
  To assess whether spontaneous acceptance might be the consequence of a T cell help deficit at the time of the first exposure of alloantigens to the host, we studied the effect of exogenous interleukin (IL)-2 injections at the time of liver transplantation and during long-term follow-up.
  
  
  RESULTS
  Although spontaneous acceptance of the liver allograft constantly ensued in the DA to PVG combination, a daily injection of recombinant IL-2 (3 x 10(5) U) uniformly provoked acute cellular rejection of the liver allograft and consequently the death of animals by postoperative day 5-6. Simultaneous to the graft loss, hepatic enzymes (alanine aminotransferase) increased more than 50-fold in IL-2-treated recipients, whereas similar IL-2 treatment did not produce any hepatic dysfunction in syngeneic animals. By immunohistology, the expression of the alpha chain of the IL-2 receptor, usually undetectable in untreated animals, was evident on CD4 and CD8 lymphocytes infiltrating the liver graft. In contrast, a similar IL-2 regimen and even higher IL-2 doses (x 10(6) U) did not abrogate the liver allograft survival during long-term follow-up.
  
  
  CONCLUSIONS
  Our results demonstrate that spontaneous rat liver allograft acceptance may be abolished by exogenous IL-2 injections, which suggests that an "inherent T cell help deficit" might be implicated in the spontaneous acceptance mechanisms of DA to PVG liver allografts.
authors.affiliation: Laboratory of Experimental Surgery, University of Louvain Medical School, Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Delrivière
authors.forename: X
authors.initials: X
authors.lastname: Havaux
authors.forename: D
authors.initials: D
authors.lastname: Latinne
authors.forename: H
authors.initials: H
authors.lastname: Bazin
authors.forename: N
authors.initials: N
authors.lastname: Kamada
authors.forename: B
authors.initials: B
authors.lastname: Nordlinger
authors.forename: P
authors.initials: P
authors.lastname: Gianello
mesh_terms: D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins; D000410:Alanine Transaminase