Expression of the cytotoxic T cell mediator granzyme B during liver allograft rejection.

Cytotoxic T lymphocytes (CTL) constitute a major component of the alloreactive response following organ transplantation. The molecular mechanisms of CTL killing remain to be determined but multiple candidate molecules involved in CTL-mediated cytotoxicity have been identified. Granzyme B, a serine protease, participates in perforin-dependent pathways of cytotoxicity and is necessary for induction of DNA fragmentation in target cells. In this study the expression of granzyme B in liver biopsies obtained from liver allograft recipients was determined by semiquantitative reverse transcriptase polymerase chain reaction. Biopsies were classified into four groups--no evidence of rejection, preservation injury, acute rejection, or resolving rejection--according to histopathological criteria. There was a significantly higher frequency of transcripts for granzyme B in the acute rejection group (82.8%) compared to the no rejection (20.0%), resolving rejection (12.5%) and preservation injury (0%) groups. Analysis of granzyme B gene expression in sequential samples from individual patients prior to, and after, treatment for rejection revealed an inverse correlation between granzyme B mRNA and response to treatment. These findings indicate that the cytopathic mediator granzyme B may participate in CTL-mediated cytotoxicity during liver allograft rejection.