The role of the c-kit proto-oncogene in organ allograft rejection is not kn
own. We investigated the level of c-kit expression following allogeneic tra
nsplantation of ACI rat liver grafts into LEW recipients. We studied c-kit
mRNA and protein expression in groups of transplant recipients receiving he
patic isografts, hepatic allografts, or hepatic allografts after donor-spec
ific blood transfusion (DST). Pretransplantation DST significantly prolonge
d survival of hepatic allografts. Infiltrates expressing c-kit were observe
d in allografts to untreated rats but not in groups receiving isografts or
allografts following DST. Northern analysis also demonstrated abundant c-ki
t mRNA transcripts in the untreated allograft group in contrast to the isog
raft and the DST-treated groups. In addition, significantly more transcript
s for interleukin-12 (IL-12), which is synergistic with c-kit, were present
in untreated than in DST-treated allograft groups. In contrast, transformi
ng growth factor beta (TGF-beta), which inhibits c-kit synthesis, was expre
ssed abundantly in hepatic allografts to DST-treated rats but not in allogr
afts to untreated animals. Transcripts for IL-10, which inhibits IL-12 prod
uction, were significantly more plentiful in hepatic allografts following D
ST than in those without DST. The results suggest that c-kit proto-oncogene
expression in infiltrating cells is associated with rat hepatic allograft
rejection.