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Abstract The aim of the work is: 1- To identify the profile of cytokine mRNA expression in liver allograft and in peripheral blood mononuclear cells (PBMC) from long term liver recipients and investigating the role of immunosuppressive cytokines in creating a state of tolerance in vivo. 2- To establish whether an alternation in the balance between TH1 and TH2 cytokines might be responsible for the maintenance of tolerance. 3- To examine whether the preferential induction of TH2 may be beneficial in induction of tolerance in liver transplantation. 4- To identify the role of TH1/TH2 paradigm in liver transplantation tolerance. 5- To test the hypothesis that selective Th1 activation is associated with rejection and selective Th2 activation is associated with the induction of tolerance. We have used the semi quantitative reverse transcription polymerase chain reaction (RT-PCR) to assess the involvement of T helper cell subsets in liver allograft rejection and tolerance by determining cytokine mRNA profile to each subset in the graft and peripheral lymphocytes of liver allograft recipients. From this study we conclude that: 1- Semi quantitative analysis of cytokine mRNA by reverse transcription polymeras chain reaction is a useful and sensitive method for the study of liver allograft rejection and tolerance and the technique may become an important tool in future studies of cytokine mediated immune responses in liver transplantation. 2- Inflammatory and immunoregulatory cytokines are produced within the allograft and are important local regulators in mechanisms of rejection and tolerance in liver transplantation. 3- PCR-based assay was capable of simultaneous analysis of multiple cytokine transcripts (mRNA) directly from tissue samples. 4- In peripheral blood, the increase in Th2 cytokine mRNA, along with evidence with increased intragraft Th2 cytokine mRNA implies that it has a role in the development of liver transplantation tolerance. 5- Cytokine-mediated immune dysregulation may be a mechanism of tolerance after orthotopic liver transplantation. 6- RT-PCR technique is likely to have a major impact on the study of molecular biology of liver allograft. 7- A switch from a Th1 to Th2 program is critical to tolerance induction. 8- High levels of mRNA for both IL-4 and IL-10 are responsible for induction and/ or maintenance of tolerance in liver transplantation. |