<i>Batf3</i> Deficiency Reveals a Critical Role for CD8α ⁺ Dendritic Cells in Cytotoxic T Cell Immunity

TLDR

In vitro studies indicate that CD8α+ dendritic cells mediate antigen cross‑presentation, but in vivo analysis has been limited by the absence of systems that selectively eliminate this lineage. This study aims to elucidate the role of CD8α+ dendritic cells in immunity by deleting the transcription factor Batf3. Deletion of Batf3 ablates CD8α+ dendritic cell development, enabling in vivo examination of their function. Batf3‑/‑ mice display defective cross‑presentation, lack virus‑specific CD8+ T cell responses to West Nile virus, and exhibit impaired rejection of highly immunogenic syngeneic tumors, highlighting the essential role of CD8α+ dendritic cells in viral and tumor immunity.

Abstract

Although in vitro observations suggest that cross-presentation of antigens is mediated primarily by CD8alpha+ dendritic cells, in vivo analysis has been hampered by the lack of systems that selectively eliminate this cell lineage. We show that deletion of the transcription factor Batf3 ablated development of CD8alpha+ dendritic cells, allowing us to examine their role in immunity in vivo. Dendritic cells from Batf3-/- mice were defective in cross-presentation, and Batf3-/- mice lacked virus-specific CD8+ T cell responses to West Nile virus. Importantly, rejection of highly immunogenic syngeneic tumors was impaired in Batf3-/- mice. These results suggest an important role for CD8alpha+ dendritic cells and cross-presentation in responses to viruses and in tumor rejection.