T_H2 Predominant Immune Responses Prevail in Human Abdominal Aortic Aneurysm

T lymphocytes localize within lesions of two diametrically opposed expressions of atherosclerosis: stenosis-producing plaques and ectasia-producing abdominal aortic aneurysm (AAA). T_H1 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_H2-associated cytokines and correspondingly lack mediators associated with the T_H1 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_H1 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-γ-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-γ, although both types of lesions contained this T_H1-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.