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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2206.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Chronic Immune Reactivity Against Persisting Microbial Antigen in the Vasculature Exacerbates Atherosclerotic Lesion Formation

Philippe Krebs; Elke Scandella; Beatrice Bolinger; Daniel Engeler; Simone Miller; Burkhard Ludewig

From the Research Department, Kantonal Hospital St Gallen, St Gallen, Switzerland.

Correspondence to Burkhard Ludewig, Research Department, Kantonsspital St Gallen, Rorschacherstrasse 95, CH-9007 St Gallen, Switzerland. E-mail burkhard.ludewig{at}kssg.ch

Objective— The purpose of this study was to examine the relative contribution of different immunopathological mechanisms during murine cytomegalovirus (MCMV)-mediated acceleration of atheroma formation in apolipoprotein E–deficient (apoE^–/–) mice.

Methods and Results— To distinguish between the effects of systemic activation and cognate immune reactivity against a pathogen-derived persisting antigen in the vasculature, we used hypercholesterolemic transgenic mice constitutively expressing the β-galactosidase (β-gal) transgene in the cardiovascular system (apoE^–/–xSM-LacZ). After infection with β-gal–recombinant MCMV-LacZ, apoE^–/–, and apoE^–/–xSM-LacZ mice mounted comparable cellular immune responses against the virus. β-gal–specific CD8⁺ T cells expanded rapidly and remained detectable for at least 100 days in both mouse strains. However, compared with apoE^–/– mice, apoE^–/–xSM-LacZ mice developed drastically accelerated atherosclerosis. Moreover, atherosclerotic lesions in MCMV-LacZ–infected apoE^–/–xSM-LacZ but not apoE^–/– mice were associated with pronounced inflammatory infiltrates.

Conclusions— Taken together, our data indicate that chronic immune reactivity against pathogen-derived antigens persisting in the vasculature significantly exacerbates atherogenesis.

This study demonstrates that T cell responses directed against persisting microbial antigen within the vasculature favor the development of an inflammatory environment that is important for the acceleration of atherosclerotic lesion development.

Key Words: cytomegalovirus • atherosclerosis • inflammation • immunopathology • coronary heart disease