Larsen C P, Ritchie S C, Hendrix R, Linsley P S, Hathcock K S, Hodes R J, Lowry R P, Pearson T C
Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322.
J Immunol. 1994 Jun 1;152(11):5208-19.
Dendritic cells (DC) play a critical role in the initiation of T cell-mediated immune responses, and express costimulatory molecules that are required for optimal activation of unprimed T cells. Studies on the regulation of the costimulatory molecules on DC have produced evidence from several systems that GM-CSF can up-regulate expression of CTLA4 counter receptor (CTLA4-CR) (but not intercellular adhesion molecule 1 (ICAM-1) and heat stable Ag (HsAg)) on DC. This is demonstrated on splenic DC, Langerhans cells, kidney DC in culture, and in a skin-explant culture system, in which the increased expression of CTLA4-CR on Langerhans cells (LC) occurs concomitantly with their migration out of skin. Interestingly, despite the ability of both GM-CSF and IFN-gamma to increase CTLA4-CR and maintain similar levels of ICAM-1, HsAg, and MHC molecule expression, the functional consequences of these cytokines on splenic DC are distinctly different. GM-CSF enhances the ability of DC to stimulate both T cell proliferation and cytokine release, whereas IFN-gamma causes no increase in immunostimulatory function. Further analysis of the CTLA4-CR on these cell populations by using the GL-1 and IG10 mAbs has shown that GM-CSF-cultured DC express high levels of both B7-1 and B7-2, whereas IFN-gamma-cultured DC express increased levels of only B7-2. These results suggest that optimal stimulation of unprimed T cells to proliferate and release cytokines may require participation of both of these CTLA4 counter receptors, and confirm the importance of GM-CSF for the maturation of DC into potent stimulators of T cell activation.
树突状细胞（DC）在T细胞介导的免疫反应启动过程中发挥关键作用，并表达共刺激分子，这些分子是未致敏T细胞最佳激活所必需的。对DC上共刺激分子调控的研究已从多个系统中获得证据，表明GM-CSF可上调DC上CTLA4反受体（CTLA4-CR）的表达（但不包括细胞间黏附分子1（ICAM-1）和热稳定抗原（HsAg））。这在脾DC、朗格汉斯细胞、培养的肾DC以及皮肤外植体培养系统中得到了证实，在该系统中，朗格汉斯细胞（LC）上CTLA4-CR表达的增加与其从皮肤中迁出同时发生。有趣的是，尽管GM-CSF和IFN-γ都有能力增加CTLA4-CR并维持相似水平的ICAM-1、HsAg和MHC分子表达，但这些细胞因子对脾DC的功能影响却明显不同。GM-CSF增强了DC刺激T细胞增殖和细胞因子释放的能力，而IFN-γ并未增加免疫刺激功能。通过使用GL-1和IG10单克隆抗体对这些细胞群体上的CTLA4-CR进行进一步分析表明，GM-CSF培养的DC高水平表达B7-1和B7-2，而IFN-γ培养的DC仅增加B7-2的表达水平。这些结果表明，未致敏T细胞增殖和释放细胞因子的最佳刺激可能需要这两种CTLA4反受体的参与，并证实了GM-CSF对于DC成熟为T细胞激活的有效刺激剂的重要性。
