Hypothesis Dendritic cells and the mode of action of anticalcineurinic drugs: an integrating hypothesis

Despite important advances in the understanding of the immunobiology of allotransplantation and the mecha-nism of action of immunosuppressive drugs, recent reports have challenged our current understanding of these phenomena. Until now, the mode of action of cyclosporin A (CsA) and tacrolimus (FK506) has been mainly ascribed to their remarkable capacity to act upon T lymphocytes by inhibiting the production of IL-2 and IFN-g, two cytokines required for the initiation and maintenance of T-lymphocyte responses in allograft rejection [1–3]. It is well recognized that immunosuppressive drugs such as CsA and FK506 act by inhibiting calcineurin activity. Calcineurin is a phosphatase that activate