T(H)2 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(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.
Schönbeck
Uwe
U
Leducq Center for Cardiovascular Research, Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. uschoenbeck@rics.bwh.harvard.edu
Sukhova
Galina K
GK
Gerdes
Norbert
N
Libby
Peter
P
D017544:Aortic Aneurysm, Abdominal / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines