T cell function is dispensable for intracranial aneurysm formation and progression.
T cell function is dispensable for intracranial aneurysm formation and progression.
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DOI：
10.1371/journal.pone.0175421
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Aoki T
中科院分区：
文献类型：
--
作者：
Miyata H;Koseki H;Takizawa K;Kasuya H;Nozaki K;Narumiya S;Aoki T
鉴于颅内动脉瘤作为致死性蛛网膜下腔出血的主要原因的社会重要性，阐明其发病机制对于改善破裂后的不良预后至关重要。先前对人类动脉瘤壁的组织病理学分析显示，病变中存在T细胞，提示这种类型的细胞参与了发病机制。然而，目前尚不清楚T细胞是否积极参与了颅内动脉瘤的进展。采用大鼠颅内动脉瘤模型，探讨T细胞是否参与了动脉瘤的发生发展。在这个模型中，动脉瘤是由于颅内动脉分叉处的血流动力增加而导致的，在那里发生了动脉瘤。该模型采用了T细胞缺陷和药物抑制T细胞功能的方法。CD3阳性T细胞存在于人动脉瘤壁上，其数量明显多于对照动脉壁。大鼠T细胞缺陷和口服环孢素A对T细胞功能的药理抑制均未能影响颅内动脉瘤的进展、动脉壁退行性改变和病变内巨噬细胞的浸润。虽然在颅内动脉瘤壁上可以检测到T细胞，但它们的功能对于巨噬细胞介导的炎症和动脉壁的退行性变化是必不可少的，这可能会导致颅内动脉瘤的进展。
Given the social importance of intracranial aneurysm as a major cause of a lethal subarachnoid hemorrhage, clarification of mechanisms underlying the pathogenesis of this disease is essential for improving poor prognosis once after rupture. Previous histopathological analyses of human aneurysm walls have revealed the presence of T cells in lesions suggesting involvement of this type of cell in the pathogenesis. However, it remains unclear whether T cell actively participates in intracranial aneurysm progression. To examine whether T cell is involved in aneurysm progression, intracranial aneurysm model of rat was used. In this model, aneurysm is induced by increase in hemodynamic force loaded on bifurcation site of intracranial arteries where aneurysms are developed. Deficiency in T cells and pharmacological inhibition of T cell function were applied to this model. CD3-positive T cells were present in human aneurysm walls, whose number was significantly larger compared with that in control arterial walls. Deficiency in T cells in rats and pharmacological inhibition of T cell function by oral administration of Cyclosporine A both failed to affect intracranial aneurysm progression, degenerative changes of arterial walls and macrophage infiltration in lesions. Although T cells are detectable in intracranial aneurysm walls, their function is dispensable for macrophage-mediated inflammation and degenerative changes in arterial walls, which presumably leads to intracranial aneurysm progression.