TH2 predominant immune responses prevail in human abdominal aortic aneurysm
TH2 predominant immune responses prevail in human abdominal aortic aneurysm
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DOI：
10.1016/s0002-9440(10)64206-x
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发表时间：
2002-08-01
影响因子：
6
通讯作者：
Libby, P
中科院分区：
文献类型：
--
作者：
Schönbeck, U;Sukhova, GK;Libby, P
T淋巴细胞定位于两种截然相反的动脉粥样硬化表现的病变内：狭窄产生的斑块和扩张产生的腹主动脉瘤（AAA）。T（H）1免疫反应似乎在人类狭窄病变中占主导地位。然而，关于AAA中T细胞浸润的性质的信息很少。我们在这里证明，AAAs主要表达T（H）2相关的细胞因子，相应地缺乏与T（H）1反应相关的介质，如通过Western印迹和免疫组织化学分析所确定的。特别是，动脉瘤组织表达白细胞介素（IL）-4，IL-5和IL-10，这些细胞因子在非病变组织或狭窄动脉粥样硬化中未检测到或仅微弱检测到。相比之下，AAA含有低水平的T，I特征性细胞因子IL-2和IL-15，其在狭窄病变中充分表达。值得注意的是，狭窄病变（而非AAA）含有成熟形式的干扰素-γ诱导细胞因子IL-12和IL-18以及IL-18加工酶caspase-1。此外，淋巴瘤组织缺乏γ-干扰素受体，尽管两种类型的病变都含有这种T（H）1促进细胞因子。这些研究结果表明，T细胞的功能库不同狭窄和动脉粥样硬化病变，并提供了一个新的框架，了解这些截然相反的动脉粥样硬化的表达机制。
T lymphocytes localize within lesions of two diametrically opposed expressions of atherosclerosis: stenosis-producing plaques and ectasia-producing abdominal aortic aneurysm (AAA). T(H)1 immune responses appear to predominate in human stenotic lesions. However, little information exists regarding the nature of the T-cell infiltrate in AAAs. We demonstrate here that AAAs predominantly express T(H)2-associated cytokines and correspondingly lack mediators associated with the T(H)1 response as determined by Western blot and immunohistochemical analysis. In particular, aneurysmal tissue expressed interleukin (IL)-4, IL-5, and IL-10, cytokines not or only faintly detected in nondiseased tissue or stenotic atheroma. In contrast, AAAs contained low levels of the T,I characteristic cytokines IL-2 and IL-15, which are amply expressed in stenotic lesions. Notably, stenotic lesions, but not AAAs, contained mature forms of the interferon-gamma-inducing cytokines IL-12 and IL-18 as well as the IL-18-processing enzyme caspase-1. Moreover, aneurysmal tissue lacked the receptor for interferon-gamma, although both types of lesions contained this T(H)1-promoting cytokine. These findings suggest that the functional repertoire of T cells differs in stenotic and aneurysmal lesions, and provide a novel framework for understanding the mechanisms of these diametrically opposite expressions of atherosclerosis.