ORGAN-SPECIFIC T-CELL GROWTH FACTOR AND CTL GENE ACTIVATION IN RENAL AND LIVER TRANSPLANT REJECTION

Abstract

965 Recent studies have defined the pattern of intragraft gene expression in acute rejection (AR) and other causes of graft dysfunction (NonR) in clinical renal transplantation (RTX). Fewer data exist on liver, heart or lung transplants and the impact of tissue-specific ligands and mediators on the activation of graft infiltrating cells remains unknown. We have compared the intragraft gene expression of T-cell growth factors and CTL effector genes in 39 renal transplant biopsies and 64 specimens from 14 liver transplant (LTX) recipients (57 sequential fine needle aspirates TAC and 7 additional liver biopsies) utilizing previously developed competitive RT-PCR techniques (PNAS 97:695-700). All TAC aspirates contained hepatocytes and graft infiltrating cells and were divided für RT-PCR and TCI score analysis. Unlike in RTX IL-7 or IL-15 gene expression was not detectable in AR in LTX and was very rarely seen in severe organ necrosis or sepsis in NonR LTX. IL-4, previously incriminated in AR in LTX patients, was not detectable in any sample. CTL genes were similarly expressed in RTX and LTX in AR, while NonR samples in LTX showed no CTL gene activation. Our study proves, that a single TAC can be adequately evaluated by both cell count and RT-PCR, enhancing the diagnostic capacity of fine needdle aspiration techniques. Renal and liver transplant patients show organ specific differences of rejection associated mediators that have to be acknowledged in the interpretation of PCR results. We speculate, that the absence of tissue derived IL-7 and/or IL-15 gene expression in LTX contributes to the clinically observed phenomenon of less frequent/less severe AR episodes as compared to RTX. (Table)Table