P478 * Ablation of CD8+ dendritic cell mediated cross presentation does not impact atherosclerosis in LDLR deficient mice

Background: Dendritic cells (DCs) are professional antigen presenting cells, essential in linking innate to adaptive immunity. In particular CD8+ DCs can acquire exogenous antigens for direct presentation on MHC I molecules to CD8+ T cells, a process known as cross presentation. The importance of this process is well established in the field of tumor immunology, where CD8+ DCs take up necrotic material and prime CD8+ T cells to kill tumor cells. Although all important players for cross presentation are present in advanced atherosclerosis, little is known regarding its contribution to the pathophysiology of this disease. We therefore sought to investigate this by a loss-of-function approach using batf3-/- chimeric mice, which specifically lack CD8+DCs. Methods: LDLR-/- mice were transplanted with either batf3-/- or wt bone marrow and after recovery, put on a western type diet (WTD) for 10 weeks. Histology was performed on aortic arch and root sections, while blood and lymphoid organs were analyzed by flow cytometry. Cross presentation capacity was investigated using the CD8+ OT-I T cell- actmOVA model. Results: Hematopoietic batf3 deficiency sharply decreased CD8+DC numbers in spleen and mesenteric LNs (>80% compared to WT transplanted controls; P<0.001). Concordant with this reduction, batf3-/- transplanted mice had a 75% reduction in OT-I cross-priming capacity in vivo, establishing the significance of this subset for OVA cross-presentation, even in hyperlipidemia. Furthermore, batf3-/- transplanted mice did not show lower CD8+ T cell numbers, nor did batf3 deficiency have an effect on CD4+ T cell numbers or on other leukocyte subsets. Surprisingly, despite the dampened cross presentation capacity, batf3-/- mice had unchanged atherosclerosis burden and plaque progression in the aortic arch and root. Likewise, plaque T cell infiltration or cell death did not differ between batf3-/- and WT transplanted mice, as assessed by CD3 and caspase 3 staining, respectively. Conclusion: While CD8+DC loss during atherosclerosis development profoundly reduces cross priming ability, it does not notably affect activation status or numbers of other leukocyte populations nor does it influence lesion development in WTD fed LDLR-/- mice. Taken together, our data clearly demonstrate that CD8+ DCs do not significantly contribute to atherosclerotic plaque formation and stability.