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IN SITU EXPRESSION OF TUMOR NECROSIS FACTOR‐ALPHA, INTERFERON‐GAMMA, AND INTERLEUKIN‐2 RECEPTORS IN RENAL ALLOGRAFT BIOPSIES

The production and release of cytokines and their receptors are of critical importance in mediating graft injury. In order to evaluate the expression of cytokines in renal allograft biopsies, we performed immunocytochemical studies to detect activated cells positive for TNF-α, IFN-γ, and IL-2R, using an alkaline phosphatase anti–alkaline phosphatase technique (APAAP). Sixty-one biopsy specimens from renal transplant patients were analyzed and were classified according to both clinical and conventional morphological criteria. There was a significant correlation between the number of positive cells reactive with monoclonal antibodies directed against TNF-α, IFN-γ, and IL-2R and the presence of acute cellular rejection. The mean number of infiltrating cells (cells/mm2) positive for TNF-α (9.2± 1.1), IFN-γ (6.7±1.7), and IL-2R (31.2±4.8) was significantly greater in acute cellular rejection episodes compared with nonrejecting kidneys (0.9±0.2, 1.2±0.4, and 8.8±2.9 positive cells/mm2 for TNF-α, IFN-γ, and IL-2R, respectively). No significant expression of these cytokines was found in the majority of biopsies with chronic rejection. In two cases, in which acute cellular rejection was not sustained on clinical grounds but was diagnosed on histology, the expression of TNF-α, IFN-γ, and IL-2R was similar to that observed in typical cellular rejection. We conclude that TNF-α, IFN-γ, and IL-2R are markedly expressed by activated mononuclear infiltrating cells in acute cellular rejection, and that these cytokines play an important role in allograft rejection. The immunocytochemical evaluation of cytokine expression is a simple and rapid method that is helpful in differentiating acute cellular rejection from other causes of graft disfunction.