De Smedt T, Van Mechelen M, De Becker G, Urbain J, Leo O, Moser M
Département de Biologie Moléculaire, Université Libre de Bruxelles, Rhode-Saint-Genèse, Belgium.
Eur J Immunol. 1997 May;27(5):1229-35. doi: 10.1002/eji.1830270526.
The main function of dendritic cells (DC) is to induce the differentiation of naive T lymphocytes into helper cells producing a large array of lymphokines, including interleukin (IL)-2; interferon-gamma (IFN-gamma), IL-4, IL-5 and IL-10. The potent immunostimulatory properties of DC develop during a process of maturation that occurs spontaneously in vitro. Since IL-10 has been shown to inhibit Th1 responses, we determined its effect on DC maturation and accessory function. Our data show that DC that have undergone maturation in vitro in the presence of IL-10, have an impaired capacity to induce a Th1-type response in vivo, leading to the development of Th2 lymphocytes. Their inability to promote the synthesis of IFN-gamma seems to correlate with a decreased production of IL-12, an heterodimeric cytokine necessary for optimal generation of Th1-type cells. These results suggest that IL-10 skews the Th1/Th2 balance to Th2 in vivo by selectively blocking IL-12 synthesis by the antigen-presenting cells that play a role of adjuvant of the primary immune response. The cytokines present in the environment at the presentation step may, therefore, determine the class of the immune response induced by DC in vivo, i.e. Th0, Th1 and/or Th2.
树突状细胞(DC)的主要功能是诱导未成熟的T淋巴细胞分化为能产生大量淋巴因子的辅助细胞,这些淋巴因子包括白细胞介素(IL)-2、γ干扰素(IFN-γ)、IL-4、IL-5和IL-10。DC强大的免疫刺激特性在体外自发发生的成熟过程中形成。由于IL-10已被证明可抑制Th1反应,我们研究了其对DC成熟及辅助功能的影响。我们的数据表明,在IL-10存在的情况下于体外成熟的DC,在体内诱导Th1型反应的能力受损,导致Th2淋巴细胞的发育。它们无法促进IFN-γ的合成似乎与IL-12产生减少有关,IL-12是Th1型细胞最佳生成所必需的异二聚体细胞因子。这些结果表明,IL-10通过选择性地阻断在初次免疫反应中起佐剂作用的抗原呈递细胞合成IL-12,在体内使Th1/Th2平衡偏向Th2。因此,在呈递步骤时环境中存在的细胞因子可能决定DC在体内诱导的免疫反应类型,即Th0、Th1和/或Th2。