Monocyte-Derived Dendritic Cells Dictate the Memory Differentiation of CD8⁺ T Cells During Acute Infection

Monocyte-derived dendritic cells (moDCs) have been shown to robustly expand during infection; however, their roles in anti-infectious immunity remain unclear. Here, we found that moDCs were dramatically increased in the secondary lymphoid organs during acute LCMV infection in an interferon-γ (IFN-γ)-dependent manner. We also found that priming by moDCs enhanced the differentiation of memory CD8⁺ T cells compared to differentiation primed by conventional dendritic cells (cDCs) through upregulation of Eomesodermin (Eomes) and T cell factor-1 (TCF-1) expression in CD8⁺ T cells. Consequently, impaired memory formation of CD8⁺ T cells in mice that had reduced numbers of moDCs led to defective clearance of pathogens upon rechallenge. Mechanistically, attenuated interleukin-2 (IL-2) signaling in CD8⁺ T cells primed by moDCs was responsible for the enhanced memory programming of CD8⁺ T cells. Therefore, our findings unveil a specialization of the antigen-presenting cell subsets in the fate determination of CD8⁺ T cells during infection and pave the way for the development of a novel therapeutic intervention on infection.