Interleukin‐12 is produced by dendritic cells and mediates T helper 1 development as well as interferon‐γ production by T helper 1 cells

作者：Christine Heufler, Franz Koch, Ursula Stanzl, Gerda Topar, Maria Wysocka, Giorgio Trinchieri, Alexander Enk, Ralph M. Steinman, Nikolaus Romani, Gerold Schuler · 发表于：European Journal of Immunology · 年份：1996 · DOI：10.1002/eji.1830260323 · 被引用次数：707 · 研究领域：Immunotherapy and Immune Responses、T-cell and B-cell Immunology、Immune Cell Function and Interaction

Interleukin-12 (IL-12), a 70-kDa heterodimeric cytokine composed of covalently linked p35 and p40 chains, is to date the most critical factor for skewing the immune response towards a T helper 1 (Th1) of cytokine profile [high interferon-gamma (IFN-gamma), low IL-4]. Established sources of IL-12 are stimulated macrophages, neutrophils and B cells. As dendritic cells (DC) process antigen in the periphery and then migrate to lymphoid organs to sensitize T cells and induce cell mediated immunity, we reasoned that DC should constitute a critical source of IL-12. The criteria used to detect IL-12 in DC were the demonstration of p40 and p35 mRNA (semiquantitative polymerase chain reaction, northern blotting, and in situ hybridization) as well as IL-12 protein (p70 enzyme-linked immunosorbent assay, p70 antigen capture followed by IFN-gamma bioassay, free p40 chain radioimmunoassay or immunoprecipitation). We found that conventional stimuli such as Staphylococcus aureus induced production of IL-12 by murine as well as human DC in amounts comparable to spleen cells, peritoneal macrophages or peripheral mononuclear cells. DC exhibited, however, features that had not been seen with other antigen-presenting cells: they produced bioactive IL-12 upon antigen-specific interaction with T cells without any other stimuli; in an allogeneic mixed leukocyte reaction model, neutralizing anti-IL-12 antibodies showed that DC-derived IL-12 was critical for optimal proliferation and IFN-gamma product...