title: CD8+ T cells mediate the athero-protective effect of immunization with an ApoB-100 peptide.
abstract: Immunization of hypercholesterolemic mice with selected apoB-100 peptide antigens reduces atherosclerosis but the precise immune mediators of athero-protection remain unclear. In this study we show that immunization of apoE (-/-) mice with p210, a 20 amino acid apoB-100 related peptide, reduced aortic atherosclerosis compared with PBS or adjuvant/carrier controls. Immunization with p210 activated CD8(+) T cells, reduced dendritic cells (DC) at the site of immunization and within the plaque with an associated reduction in plaque macrophage immunoreactivity. Adoptive transfer of CD8(+) T cells from p210 immunized mice recapitulated the athero-protective effect of p210 immunization in naïve, non-immunized mice. CD8(+) T cells from p210 immunized mice developed a preferentially higher cytolytic response against p210-loaded dendritic cells in vitro. Although p210 immunization profoundly modulated DCs and cellular immune responses, it did not alter the efficacy of subsequent T cell dependent or independent immune response to other irrelevant antigens. Our data define, for the first time, a role for CD8(+) T cells in mediating the athero-protective effects of apoB-100 related peptide immunization in apoE (-/-) mice.
authors.affiliation: Division of Cardiology, Oppenheimer Atherosclerosis Research Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Kuang-Yuh
authors.initials: KY
authors.lastname: Chyu
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhao
authors.forename: Paul C
authors.initials: PC
authors.lastname: Dimayuga
authors.forename: Jianchang
authors.initials: J
authors.lastname: Zhou
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.forename: Juliana
authors.initials: J
authors.lastname: Yano
authors.forename: Wai Man
authors.initials: WM
authors.lastname: Lio
authors.forename: Lai Fan
authors.initials: LF
authors.lastname: Chan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kirzner
authors.forename: Portia
authors.initials: P
authors.lastname: Trinidad
authors.forename: Bojan
authors.initials: B
authors.lastname: Cercek
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000627:therapeutic use; D053299:Apolipoprotein B-100 / Q000276:immunology / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000517:prevention & control*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003713:Dendritic Cells; D006937:Hypercholesterolemia / Q000628:therapy*; D007114:Immunization; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use; D020011:Protective Agents
chemical_list: D000941:Antigens; D053299:Apolipoprotein B-100; D001057:Apolipoproteins E; D010446:Peptide Fragments; D020011:Protective Agents