Cytokines regulate the capacity of CD8α+ and CD8α- dendritic cells to prime Th1/Th2 cells in vivo
Cytokines regulate the capacity of CD8α+ and CD8α- dendritic cells to prime Th1/Th2 cells in vivo
复制标题
DOI：
10.4049/jimmunol.167.8.4345
复制
发表时间：
2001-10-15
影响因子：
4.4
通讯作者：
Moser, M
中科院分区：
文献类型：
--
作者：
Maldonado-López, R;Maliszewski, C;Moser, M
先前的研究表明，树突状细胞(DC)亚类在啮齿动物和人类中指导不同的Th群体的发展。在小鼠中，我们最近发现，注射抗原冲击的CD8α(-)DC诱导Th2型反应，而注射CD8α(+)DC则导致Th1分化。为了确定参与Th反应极化的DC衍生因子，我们将从缺乏干扰素-γ、IL-4、IL-12或IL-10基因缺陷的小鼠中纯化的亚群注射到野生型动物中。在这项工作中，我们报告了CD8α(+)DC启动Th1所需的DC来源的IL-12和干扰素-γ，而CD8a-DC所需的IL-10是Th2细胞最佳发育所必需的。DC产生的IL-12水平似乎决定了体内Th1/Th2的平衡。进一步证明了DC子集的作用表现出一定的灵活性。体外用IL-10处理DC可选择性降低CD8α(+)DC的活性。相反，与干扰素-γ孵育下调CD8α(-)DC的Th2促进能力，并增加这两个亚群的Th1偏斜特性。
Prior studies have shown that subclasses of dendritic cells (DC) direct the development of distinct Th populations in rodents and in humans. In the mouse, we have recently shown that administration of Ag-pulsed CD8 alpha (-) DC induces a Th2-type response, whereas injection of CD8 alpha (+) DC leads to Th1 differentiation. To define the DC-derived factors involved in the polarization of Th responses, we injected either subset purified from mice genetically deficient for IFN-gamma, IL-4, IL-12, or IL-10 into wild-type animals. In this work, we report that DC-derived IL-12 and IFN-gamma are required for Th1 priming by CD8 alpha (+) DC, whereas IL-10 is required for optimal development of Th2 cells by CD8a- DC. The level of IL-12 produced by the DC appears to determine the Th1/Th2 balance in vivo. We further show that the function of DC subsets displays some flexibility. Treatment of DC with IL-10 in vitro induces a selective decrease in the viability of CD8 alpha (+) DC. Conversely, incubation with IFN-gamma down-regulates the Th2-promoting capacities of CD8 alpha (-) DC and increases the Th1-skewing properties of both subsets.