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

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Abstract

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.

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