Ablation of CD8α(+) dendritic cell mediated cross-presentation does not impact atherosclerosis in hyperlipidemic mice

Sci Rep. 2015 Oct 21:5:15414. doi: 10.1038/srep15414.

Abstract

Clinical complications of atherosclerosis are almost exclusively linked to destabilization of the atherosclerotic plaque. Batf3-dependent dendritic cells specialize in cross-presentation of necrotic tissue-derived epitopes to directly activate cytolytic CD8 Tcells. The mature plaque (necrotic, containing dendritic cells and CD8 Tcells) could offer the ideal environment for cross-presentation, resulting in cytotoxic immunity and plaque destabilization. Ldlr(-/-) mice were transplanted with batf3(-/-) or wt bone marrow and put on a western type diet. Hematopoietic batf3 deficiency sharply decreased CD8α(+) DC numbers in spleen and lymph nodes (>80%; P < 0,001). Concordantly, batf3(-/-) chimeras had a 75% reduction in OT-I cross-priming capacity in vivo. Batf3(-/-) chimeric mice did not show lower Tcell or other leukocyte subset numbers. Despite dampened cross-presentation capacity, batf3(-/-) chimeras had equal atherosclerosis burden in aortic arch and root. Likewise, batf3(-/-) chimeras and wt mice revealed no differences in parameters of plaque stability: plaque Tcell infiltration, cell death, collagen composition, and macrophage and vascular smooth muscle cell content were unchanged. These results show that CD8α(+) DC loss in hyperlipidemic mice profoundly reduces cross-priming ability, nevertheless it does not influence lesion development. Taken together, we clearly demonstrate that CD8α(+) DC-mediated cross-presentation does not significantly contribute to atherosclerotic plaque formation and stability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Atherosclerosis / pathology
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / pathology
  • CD8 Antigens / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Epitopes / immunology
  • Humans
  • Hyperlipidemias / genetics
  • Hyperlipidemias / immunology*
  • Hyperlipidemias / pathology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Mice
  • Plaque, Atherosclerotic / genetics
  • Plaque, Atherosclerotic / immunology*
  • Plaque, Atherosclerotic / pathology
  • Receptors, LDL / genetics
  • Repressor Proteins / genetics
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology

Substances

  • Basic-Leucine Zipper Transcription Factors
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Epitopes
  • Receptors, LDL
  • Repressor Proteins
  • SNFT protein, mouse