Costimulation Blockade in Autoimmunity and Transplantation: The CD28 Pathway.
Costimulation Blockade in Autoimmunity and Transplantation: The CD28 Pathway.
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DOI：
10.4049/jimmunol.1601135
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发表时间：
2016-09-15
期刊：
影响因子：
--
通讯作者：
Larsen CP
中科院分区：
文献类型：
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作者：
Adams AB;Ford ML;Larsen CP
T细胞活化是一个复杂的过程，需要多个细胞信号传导途径，包括初级识别信号和额外的共刺激信号。在共刺激信号不存在的情况下，TCR信号传导可导致激活尝试失败和随后的无反应性。最佳表征的共刺激途径之一包括IG超家族成员CD 28和CTLA-4及其配体CD 80和CD 86。融合蛋白CTLA-4-IG作为实验和后续治疗工具的开发是现代免疫学中的主要成功故事之一。阿巴西普和贝拉西普分别是临床上批准用于治疗类风湿性关节炎和肾移植的药剂。未来的干预措施可能包括选择性CD 28阻断以阻断CD 28的共刺激潜力，同时利用CTLA-4的共抑制作用。
T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. TCR signaling in the absence of costimulatory signals can lead to an abortive attempt at activation and subsequent anergy. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. The development of the fusion protein CTLA-4–Ig as an experimental and subsequent therapeutic tool is one of the major success stories in modern immunology. Abatacept and belatacept are clinically approved agents for the treatment of rheumatoid arthritis and renal transplantation, respectively. Future interventions may include selective CD28 blockade to block the costimulatory potential of CD28 while exploiting the coinhibitory effects of CTLA-4.