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


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.
Krebs
Philippe
P
Research Department, Kantonsspital St Gallen, Rorschacherstrasse 95, CH-9007 St Gallen, Switzerland.
Scandella
Elke
E
Bolinger
Beatrice
B
Engeler
Daniel
D
Miller
Simone
S
Ludewig
Burkhard
B
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001011:Aorta / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D006566:Herpesviridae Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D006937:Hypercholesterolemia / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007763:Lac Operon; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000276:immunology* / Q000472:pathogenicity; D013997:Time Factors; D014779:Virus Replication; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D000956:Antigens, Viral; D001057:Apolipoproteins E; C491899:Fas protein, mouse; D019014:fas Receptor; D001616:beta-Galactosidase