Publikation

Chronic immune reactivity against persisting microbial antigen in the vasculature exacerbates atherosclerotic lesion formation

Wissenschaftlicher Artikel/Review - 01.10.2007

Bereiche
PubMed
DOI

Zitation
Krebs P, Scandella E, Bolinger B, Engeler D, Miller S, Ludewig B. Chronic immune reactivity against persisting microbial antigen in the vasculature exacerbates atherosclerotic lesion formation. Arteriosclerosis, thrombosis, and vascular biology 2007; 27:2206-13.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Arteriosclerosis, thrombosis, and vascular biology 2007; 27
Veröffentlichungsdatum
01.10.2007
eISSN (Online)
1524-4636
Seiten
2206-13
Kurzbeschreibung/Zielsetzung

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 beta-galactosidase (beta-gal) transgene in the cardiovascular system (apoE-/- x SM-LacZ). After infection with beta-gal-recombinant MCMV-LacZ, apoE-/-, and apoE-/- x SM-LacZ mice mounted comparable cellular immune responses against the virus. Beta-gal-specific CD(+ T cells expanded rapidly and remained detectable for at least 100 days in both mouse strains. However, compared with apoE-/- mice, apoE-/- x SM-LacZ mice developed drastically accelerated atherosclerosis. Moreover, atherosclerotic lesions in MCMV-LacZ-infected apoE-/- x SM-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.