Mosca P J, Hobeika A C, Clay T M, Nair S K, Thomas E K, Morse M A, Lyerly H K
Departments of General and Thoracic Surgery, Pathology, Immunology, and Internal Medicine, Center for Genetic and Cellular Therapies, Duke University Medical Center, Durham, NC, USA.
Blood. 2000 Nov 15;96(10):3499-504.
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 surface 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-specific T cells. We used combinations of signaling through CD40, using CD40 ligand trimer (CD40L), and interferon gamma to demonstrate that CD83 expression is necessary but not sufficient for optimal production of IL-12 by DCs. Phenotypically mature DCs could be induced to produce high levels of IL-12 p70 only when provided 2 simultaneous stimulatory signals. By intracellular cytokine detection, we determined that only a subset of cells that express high levels of CD80 and CD83 generate large amounts of IL-12. DCs matured with both signals are superior to DCs stimulated with the individual agents in activating antigen-specific T cell in vitro. These findings have important implications regarding the identification, characterization, and clinical application of functionally mature DCs.
树突状细胞（DCs）可能起源于多个谱系，并经历一系列中间阶段直至完全成熟，此时它们能够实现最佳的抗原呈递和T细胞激活。CD83在细胞表面的高表达被认为与DCs的完全成熟相关，并且已经证明多种因子可增加DCs上CD83的表达。我们推测白细胞介素12（IL-12）的表达将是能够激活抗原特异性T细胞的功能成熟DCs的更准确标志物。我们使用通过CD40（使用CD40配体三聚体（CD40L））和干扰素γ的信号传导组合来证明，CD83的表达对于DCs最佳产生IL-12是必要的，但并不充分。只有在同时提供2个刺激信号时，表型成熟的DCs才能被诱导产生高水平的IL-12 p70。通过细胞内细胞因子检测，我们确定只有一部分表达高水平CD80和CD83的细胞会产生大量的IL-12。在体外激活抗原特异性T细胞方面，用两种信号成熟的DCs优于用单个因子刺激的DCs。这些发现对于功能成熟DCs的鉴定、表征和临床应用具有重要意义。
