Liver-resident CD103+ dendritic cells prime antiviral CD8+ T cells in situ

Abstract

The liver maintains a tolerogenic environment to avoid unwarranted activation of its resident immune cells upon continuous exposure to food and bacterially derived Ags. However, in response to hepatotropic viral infection, the liver’s ability to switch from a hyporesponsive to a proinflammatory environment is mediated by select sentinels within the parenchyma. To determine the contribution of hepatic dendritic cells (DCs) in the activation of naive CD8+ T cells, we first characterized resident DC subsets in the murine liver. Liver DCs exhibit unique properties, including the expression of CD8α (traditionally lymphoid tissue specific), CD11b, and CD103 markers. In both the steady-state and following viral infection, liver CD103+ DCs express high levels of MHC class II, CD80, and CD86 and contribute to the high number of activated CD8+ T cells. Importantly, viral infection in the Batf3−/− mouse, which lacks CD8α+ and CD103+ DCs in the liver, results in a 3-fold reduction in the proliferative response of Ag-specific CD8+ T cells. Limiting DC migration out of the liver does not significantly alter CD8+ T cell responsiveness, indicating that CD103+ DCs initiate the induction of CD8+ T cell responses in situ. Collectively, these data suggest that liver-resident CD103+ DCs are highly immunogenic in response to hepatotropic viral infection and serve as a major APC to support the local CD8+ T cell response. It also implies that CD103+ DCs present a promising cellular target for vaccination strategies to resolve chronic liver infections.