Journal of the American Heart Association 2017 07 156(7) pii e005318
T cells are found in atherosclerotic plaques, with evidence supporting a potential role for CD8+ T cells in atherogenesis. Prior studies provide evidence of low-density lipoprotein and apoB-100 reactive T cells, yet specific epitopes relevant to the disease remain to be defined. The current study was undertaken to identify and characterize endogenous, antigen-specific CD8+ T cells in atherosclerosis.
METHODS AND RESULTS
A peptide fragment of apoB-100 that tested positive for binding to the mouse MHC-I allele H2K(b) was used to generate a fluorescent-labeled H2K(b) pentamer and tested in apoE(-/-) mice. H2K(b) pentamer(+)CD8+ T cells were higher in apoE(-/-) mice fed an atherogenic diet compared with those fed a normal chow. H2K(b) pentamer (+)CD8+ T cells in atherogenic diet-fed mice had significantly increased effector memory phenotype with a shift in Vβ profile. H2K(b) pentamer blocked lytic activity of CD8+ T cells from atherogenic diet-fed mice. Immunization of age-matched apoE(-/-) mice with the apoB-100 peptide altered the immune-dominant epitope of CD8+ T cells and reduced atherosclerosis.
Our study provides evidence of a self-reactive, antigen-specific CD8+ T-cell population in apoE(-/-) mice. Immune modulation using the peptide antigen reduced atherosclerosis in apoE(-/-) mice.