SEQUENTIAL MONITORING OF PERIPHERAL T-LYMPHOCYTE CYTOKINE GENE EXPRESSION IN THE EARLY POST RENAL ALLOGRAFT PERIOD12

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Abstract
Despite numerous studies, the precise role of cytokines in acute renal allograft rejection remains unclear. In this study we have monitored sequential changes in peripheral T cell cytokine gene expression, correlating the changes with clinical events after adult renal transplantation, to provide a deeper insight of the role of cytokines in allograft rejection. Sequential changes in peripheral Th-1 [interleukin- (IL) 2 and interferon-γ] and Th-2 (IL-4, IL-5, IL-10, and IL-13) cytokine gene expression in 43 patients with (n=15) and without (n=28) episodes of biopsy-proven rejection was monitored in the first 6 weeks after renal transplantation using a sensitive, semi-quantitative reverse-transcriptase polymerase chain reaction ELISA approach. Th-2 cytokines: IL-5 and IL-13 expression increased before and during acute rejection, and decreased after successful antirejection therapy. A significant fall in IL-4 expression after transplantation and subsequent return to its baseline level of expression was observed in both nonrejectors and rejectors. IL-10 showed persistently high expression in nonrejectors, but in rejectors the expression fell during acute rejection, with a subsequent rise after antirejection therapy. Th-1 cytokines: IL-2 and IFN-γ decreased in expression in the first week posttransplant in the rejectors, at the time of acute rejection (IL-2 only) and immediately after completion of antirejection therapy. Sequential monitoring of peripheral T cell cytokine gene expression after renal transplantation detected changes in expression that correlated with episodes of acute rejection and response to antirejection therapy. This approach may be applicable in the clinical laboratory for monitoring posttransplant changes in T cell alloreactivity and immunosuppression.