CORE_SOT例析.ppt

原文研究结论：“在高危即复宁组中，患者的肾功能恢复显著比巴利昔单抗组快，疗效持久稳定” 结论：A strategy combining sirolimus with thymoglobulin for high-risk recipients leads to prompt recovery of renal function with a low risk of acute rejection episodes. * * * * * * * * 谢 谢 Steps in T-Cell–Mediated Rejection. Antigen-presenting cells of host or donor origin migrate to T-cell areas of secondary lymphoid organs. These T cells ordinarily circulate between lymphoid tissues, regulated by chemokine and sphingosine-1-phosphate (S-1-P) receptors. APCs present donor antigen to naive and central memory T cells. Some presentation of antigen by donor cells in the graft cannot be excluded (e.g., endothelial cells that activate antigen-experienced T cells). T cells are activated and undergo clonal expansion and differentiation to express effector functions. Antigen triggers T-cell receptors (TCRs) (signal 1) and synapse formation. CD80 (B7-1) and CD86 (B7-2) on the APC engage CD28 on the T cell to provide signal 2. These signals activate three signal-transduction pathways — the calcium–calcineurin pathway, the mitogen-activated protein (MAP) kinase pathway, and the protein kinase C–nuclear factork B (NFk B) pathway — which activate transcription factors nuclear factor of activated T cells (NFAT), activating protein 1 (AP-1), and NFk B, respectively. The result is expression of CD154 (which further activates APCs), interleukin-2 receptor a chain (CD25), and interleukin-2. Receptors for a number of cytokines (interleukin-2, 4, 7, 15, and 21) share the common g chain, which binds Janus kinase 3 (JAK3). Interleukin-2 and interleukin-15 deliver growth signals (signal 3) through the phosphoinositide-3-kinase (PI-3K) pathway and the molecular-targetof-rapamycin (mTOR) pathway, which initiates the cell cycle. Lymphocytes require synthesis of purine and pyrimidine nucleotides for replication, regulated by inosine monophosphate dehydrogenase (IMPDH) and dihydroorotate dehydrogenase (DHODH), respectively. Antigenexperienced T cells h