ADMINISTRATION OF EXOGENOUS INTERLEUKIN-2 ABROGATES SPONTANEOUS RAT-LIVER ALLOGRAFT ACCEPTANCE BUT DOES NOT AFFECT LONG-TERM ESTABLISHED GRAFT-SURVIVAL

Background. Spontaneous tolerance to the orthotopic liver allograft un iformly occurs in the DA (RT1(a)) to PVG (RT1(c)) rat combination desp ite a fully allogeneic barrier. Methods. To assess whether spontaneous acceptance might be the consequence of a T cell help deficit at the t ime 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 spo ntaneous acceptance of the liver allograft constantly ensued in the DA to PVG combination, a daily injection of recombinant IL-2 (3x10(5) U) uniformly provoked acute cellular rejection of the liver allograft an d consequently the death of animals by postoperative day 5-6. Simultan eous to the graft loss, hepatic enzymes (alanine aminotransferase) inc reased more than 50-fold in IL-2-treated recipients, whereas similar I L-2 treatment did not produce any hepatic dysfunction in syngeneic ani mals. By immunohistology, the expression of the cw chain of the IL-2 r eceptor, usually undetectable in untreated animals, was evident on CD4 and CD8 lymphocytes infiltrating the liver graft. In contrast, a simi lar IL-2 regimen and even higher IL-2 doses (1x10(6) U) did not abroga te the liver allograft survival during long-term follow-up. Conclusion s. Our results demonstrate that spontaneous rat liver allograft accept ance may be abolished by exogenous IL-2 injections, which suggests tha t an ''inherent T cell help deficit'' might be implicated in the spont aneous acceptance mechanisms of DA to PVG liver allografts.