New Immunosuppressive Agents

mTOR inhibitors: An overview

“…This results in activation and proliferation of T and B cells and antibody production, as well as proliferation of such nonimmune cells as fibroblasts, endothelial cells, hepatocytes, and smooth muscle cells. [7][8][9]11,[14][15][16] Briefly (Fig. 1), after signal I (Ca ϩϩ -dependent pathway) of T-cell activation and in the presence of a valid signal II (Ca ϩϩ -independent pathway), the nuclear factor of activated T cells (NFAT) is dephosphorylated after the activation of calcineurin.…”

“…15,22,26 From the described functions of TOR, it is concluded that sirolimus and RAD block Ca ϩϩ -independent T-cell activation and proliferation after cytokine stimulation and costimulatory interaction. Indirectly, the TOR inhibitors sirolimus and RAD inhibit effector functions of CD4 ϩ helper cells and CD8 ϩ cytotoxic cells, as well as the activation of monocytes and macrophages and other proinflammatory leukocytes.…”

The immunosuppressive macrolide RAD inhibits growth of human Epstein–Barr virus-transformed B lymphocytes in vitro and in vivo : A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders

“…PTLDs comprise a whole spectrum of lymphoproliferative disorders ranging from a polyclonal atypical lymphoid hyperplasia to a monoclonal, overtly malignant B cell lymphoma (1)(2)(3)(4). Less advanced forms of PTLDs respond to a decrease in the dose of the immunosuppressive agents (1,5). However, lowering the drug dose jeopardizes survival of the graft.…”

Clinical Immunosuppression

“…Many other agents are used to interfere with secondary signaling, and may therefore aid in tolerance induction [18].…”