A subset of human monocyte-derived dendritic cells expresses high levels of interleukin-12 in response to combined CD40 Ligand and interferon-gamma treatment

Dendritic cells (DCs) may arise from multiple lineages and progress through a series of intermediate stages until fully mature, at which time they are capable of optimal antigen presentation and T-cell activation. High cell s urface expression of CD83 is presumed to correlate with full maturation of DCs, and a number of agents have been shown to increase CD83 expression on DCs, We hypothesized that interleukin 12 (IL-12) expression would be a more accurate marker of functionally mature DCs capable of activating antigen-s pecific T cells. We used combinations of signaling through CD40, using CD40 ligand trimer (CD40L), and interferon gamma to demonstrate that CD83 expre ssion is necessary but not sufficient for optimal production of IL-12 by DC s, Phenotypically mature DCs could be induced to produce high levels of IL- 12 p70 only when provided 2 simultaneous stimulatory signals. By intracellu lar cytokine detection, we determined that only a subset of cells that expr ess high levels of CD80 and CD83 generate large amounts of IL-12, DCs matur ed with both signals are superior to DCs stimulated with the individual age nts in activating antigen-specific T cell in vitro. These findings have imp ortant implications regarding the identification, characterization, and cli nical application of functionally mature DCs, (C) 2000 by The American Soci ety of Hematology.