Inhibition and genetic ablation of the B7/CD28 T-cell costimulation axis prevents experimental hypertension.
Inhibition and genetic ablation of the B7/CD28 T-cell costimulation axis prevents experimental hypertension.
复制标题
B7/CD28 T细胞共刺激轴的抑制和遗传消融可防止实验性高血压。
DOI：
10.1161/circulationaha.109.930446
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发表时间：
2010-12-14
期刊：
影响因子：
37.8
通讯作者：
Guzik TJ
中科院分区：
文献类型：
--
作者：
Vinh A;Chen W;Blinder Y;Weiss D;Taylor WR;Goronzy JJ;Weyand CM;Harrison DG;Guzik TJ
高血压的发病机制仍然知之甚少，治疗往往不成功。最近的证据表明，适应性免疫反应在这种疾病中起着重要作用。各种高血压刺激引起T细胞活化并浸润到靶器官如血管和肾脏中，促进血管功能障碍和血压升高。传统上，T细胞活化需要T细胞受体连接和共刺激。后者通常涉及抗原呈递细胞上的B7配体（CD 80和CD 86）与T细胞共受体CD 28之间的相互作用。因此，本研究旨在研究该途径在高血压中的作用。血管紧张素II诱导的高血压增加了次级淋巴组织中活化的（CD 86+）树突状细胞的存在。用CTLA 4-IG阻断B7依赖性共刺激可降低血管紧张素II和DOCA盐诱导的高血压。CTLA 4-IG可抑制这些高血压刺激引起的循环T细胞活化、T细胞细胞因子产生和血管T细胞蓄积。此外，在缺乏B7配体的小鼠中，血管紧张素II引起最小的血压升高和血管炎症，这些作用通过移植野生型骨髓而恢复。通过B7配体的T细胞共刺激对于实验性高血压的发展是必不可少的，并且抑制该过程可能在治疗该疾病中具有治疗益处。
The pathogenesis of hypertension remains poorly understood and treatment is often unsuccessful. Recent evidence suggests that the adaptive immune response plays an important role in this disease. Various hypertensive stimuli cause T cell activation and infiltration into target organs such as the vessel and the kidney, promoting vascular dysfunction and blood pressure elevation. Classically, T cell activation requires T cell receptor ligation and costimulation. The latter often involves interaction between B7 ligands (CD80 and CD86) on antigen presenting cells with the T cell co-receptor CD28. This study was therefore performed to examine the role of this pathway in hypertension. Angiotensin II-induced hypertension increased the presence of activated (CD86+) dendritic cells in secondary lymphatic tissues. Blockade of B7-dependent costimulation with CTLA4-Ig reduced both angiotensin II- and DOCA-salt induced hypertension. Activation of circulating T cells, T cell cytokine production and vascular T cell accumulation caused by these hypertensive stimuli was abrogated by CTLA4-Ig. Furthermore, in mice lacking B7 ligands, angiotensin II caused minimal blood pressure elevation and vascular inflammation, and these effects were restored by transplant with wild-type bone marrow. T cell costimulation via B7 ligands is essential for development of experimental hypertension and inhibition of this process could have therapeutic benefit in the treatment of this disease.