Schönbeck Uwe, Sukhova Galina K, Gerdes Norbert, Libby Peter
Leducq Center for Cardiovascular Research, Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Am J Pathol. 2002 Aug;161(2):499-506. doi: 10.1016/S0002-9440(10)64206-X.
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(H)1 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.
T淋巴细胞定位于动脉粥样硬化两种截然相反表现形式的病变部位:导致狭窄的斑块和导致扩张的腹主动脉瘤(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,目前所知甚少。我们在此证明,通过蛋白质印迹和免疫组织化学分析确定,AAA主要表达与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。特别是,动脉瘤组织表达白细胞介素(IL)-4、IL-5和IL-10,这些细胞因子在未患病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中T(H)1特征性细胞因子IL-2和IL-15水平较低,而这些细胞因子在狭窄病变中大量表达。值得注意的是,狭窄病变而非AAA中含有成熟形式的诱导干扰素-γ的细胞因子IL-12和IL-18以及IL-18加工酶半胱天冬酶-1。此外,动脉瘤组织缺乏干扰素-γ受体,尽管两种病变都含有这种促进T(H)1的细胞因子。这些发现表明,T细胞的功能谱在狭窄病变和动脉瘤病变中有所不同,并为理解动脉粥样硬化这两种截然相反表现形式的机制提供了一个新的框架。