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OBJECTIVES A separate subset of Granzyme B (GrB) producing B-cells regulating T-cell mediated immunity has been identified. In the present study, we investigated the role of GrB+ B-cells in renal transplant patients (RTX). METHODS 12 healthy controls (HC) and 26 RTX patients were enrolled. In addition, 19 healthy volunteers treated with cyclosporine A (CsA) were enrolled. GrB+ B-cells were determined via flow cytometry. RESULTS RTX Patients showed a diminished fraction of GrB+ B-cells as compared to HC. CsA treatment of healthy volunteers had no impact on the development of GrB+ B-cells. RTX patients with a history of allograft rejection showed an increased frequency of GrB+ B-cells. RTX patients with at least one episode of CMV viremia tended to have lower GrB+ B-cells as compared to patients without viremic episodes. CONCLUSION We demonstrate that treatment with CsA does not impair the development of GrB+ B-cells. GrB+ B-cells may have a dual role in renal transplantation as regulatory cells to maintain allospecific tolerance and as effector cells enhancing viral control.