Human dendritic cell subsets: cytokine production and their role in T-cell priming

Dendritic cells (DC) have the unique capacities to induce primary T cell responses. In mice, CD8α+DC are specialized to cross-prime CD8+ T-cells and produce IL-12 that promotes cytotoxicity. Human BDCA-3+DC share several relevant characteristics with CD8α+DC, but the capacities of human DC subsets to induce CD8+ T cell responses are incompletely understood. Here we compared CD1c+mDC1, BDCA-3+mDC2 and plasmacytoid DC (pDC) in peripheral blood and lymphoid tissues for phenotype, cytokine production and their capacities to prime cytotoxic T cells. mDC1 were surprisingly the only human DC that secreted high amounts of IL-12p70, but they required combinational Toll-like receptor (TLR) stimulation. mDC2 and pDC produced IFN-λ and IFN-α, respectively. Importantly, mDC1 and mDC2 required different combinations of TLR-ligands to cross-present protein antigens to CD8+ T cells. pDC were inefficient, and also expressed lower levels of MHC- and co-stimulatory molecules. Nevertheless, all DC induced CD8+ memory T-cell expansions upon licensing by CD4+ T cells, and primed naive CD8+ T-cells following appropriate TLR stimulation. However, since mDC1 produced IL-12 they induced the highest levels of cytotoxic molecules. In conclusion, CD1c+mDC1 are the relevant source of IL-12 for naïve T cells, and are fully equipped to cross-prime cytotoxic T cell responses.