Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses

Abstract

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 interleukin-12 (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+ myeloid DC (mDC)1, 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 interferon-l and interferon-a, 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 major histocompatibility complex 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, because mDC1 produced IL-12, they induced the highest levels of cytotoxic molecules. In conclusion, CD1c+mDC1 are the relevant source of IL-12 for naive T cells and are fully equipped to cross-prime cytotoxic T-cell responses.