on July 26, 2007
Published online before print July 26, 2007, doi: 10.1161/ATVBAHA.107.141846
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Submitted on August 21, 2006
Accepted on July 10, 2007
Chronic Immune Reactivity Against Persisting Microbial Antigen in the Vasculature Exacerbates Atherosclerotic Lesion Formation
Philippe Krebs ;
From the Research Department, Kantonal Hospital St Gallen, Gallen, Switzerland.
* To whom correspondence should be addressed. 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 
-galactosidase (-gal) transgene in the cardiovascular system (apoE-/-xSM-LacZ). After infection with -gal–recombinant MCMV-LacZ, apoE-/-, and apoE-/-xSM-LacZ mice mounted comparable cellular immune responses against the virus. -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.
Key words: cytomegalovirus • atherosclerosis • inflammation • immunopathology • coronary heart disease