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PRE AND POST TRANSPLANT IMMUNE MONITORING USING THE FLOW CYTOMETRIC CYTOKINE SECRETION ASSAY TO DETECT ALLOREACTIVE T CELLS.
Yael D. Korin, Ph.D, Clara Lee, Bs.C, Leonard Liang, MD, Albin Gritsch, MD and Elaine F. Reed, Ph.D. Los Angeles CA, University of California, Los Angeles, 90095, Immunogenetic Center, Department of Pathology.

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The direct and indirect allorecognition pathways play a role in graft rejection. To determine the contribution of the direct and indirect recognition pathways in renal allograft rejection, we have used a novel INF-g flow cytokine secretion assay for detecting alloreactivity via the direct recognition or indirect recognition pathways. Thirty-three renal allograft recipients were serially monitored, pre-transplant and at routine visits following transplantation. Five patients experienced acute cellular rejection (ACR), 2 had concurrent ACR and acute humoral rejection (AHR) and one showed only AHR. Serial studies revealed that 6 of the 7 patients with ACR showed T cell reactivity via the direct pathway prior to or at the time of rejection. Five of these seven patients also displayed T cell reactivity to donor antigens via the indirect pathway. However, indirect recognition was most often detected after the onset of ACR. All 3 patients with AHR displayed T cell alloreactivity via the indirect and direct pathways at the time of rejection. The average serum creatinine after the second month post transplantation in patients showing donor specific T cell reactivity was significantly higher than recipients without evidence of alloreactivity. This study reveals an association between T cell alloreactivity, ACR, AHR and early graft dysfunction. Our findings indicate that monitoring for T cell alloreactivity identifies patients at risk of graft rejection and early graft dysfunction.