Ablation of CD8α(+) dendritic cell mediated cross-presentation does not impact atherosclerosis in hyperlipidemic mice.
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.
Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
Bart
B
Legein
Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, and the University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Edith M
EM
Janssen
Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
Thomas L
TL
Theelen
Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.|Experimental Vascular Biology, Dept. of Medical Biochemistry, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
Marion J
MJ
Gijbels
Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
Joep
J
Walraven
Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, and the University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Jared S
JS
Klarquist
Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, and the University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Cassandra M
CM
Hennies
Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
Kristiaan
K
Wouters
Experimental Vascular Biology, Dept. of Medical Biochemistry, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
Tom T P
TT
Seijkens
Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
Erwin
E
Wijnands
Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
Judith C
JC
Sluimer
Experimental Vascular Biology, Dept. of Medical Biochemistry, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.|Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilians University (LMU), Munich, Germany.
Esther
E
Lutgens
Institute for Biomedical Engineering, Dept. of Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
Martin
M
Zenke
Medical Immunology, Universitatsklinikum Erlangen, Erlangen, Germany.
Kai
K
Hildner
Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
Erik A L
EA
Biessen
Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
Lieve
L
Temmerman
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D016827:CD8 Antigens / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011973:Receptors, LDL / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D000939:Epitopes; D011973:Receptors, LDL; D012097:Repressor Proteins; C533289:SNFT protein, mouse