Polarization of naive T cells into Th1 or Th2 by distinct cytokine-driven murine dendritic cell populations: implications for immunotherapy
Polarization of naive T cells into Th1 or Th2 by distinct cytokine-driven murine dendritic cell populations: implications for immunotherapy
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DOI：
10.1189/jlb.1104631
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发表时间：
2005-09-01
影响因子：
5.5
通讯作者：
Morel, PA
中科院分区：
文献类型：
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作者：
Feili-Hariri, M;Falkner, DH;Morel, PA
树突状细胞（DC）活化T细胞并调节其分化为T辅助细胞1型（Th 1）和/或Th 2细胞。为了鉴定具有不同能力的DC以指导Th 1/Th 2细胞分化，我们在粒细胞巨噬细胞集落刺激因子（GM）、GM +白细胞介素（IL）-4或GM + IL-15中培养小鼠骨髓祖细胞，并产生三种不同的DC群体。GM + IL-4 DC表达高水平的CD 80/CD 86和主要组织相容性复合物（MHC）II类，产生低水平的IL-12 p70。GM和GM + IL-15 DC表达低水平的CD 80/CD 86和MHC II类。GM + IL-15 DC产生高水平的IL-12 p70和干扰素（IFN）-γ，而GM DC仅产生高水平的IL-12 p70。用GM + IL-4DC刺激的幼稚T细胞除了IFN-γ外还分泌高水平的IL-4和IL-5。相比之下，GM + IL-15 DC诱导T细胞产生更高的IFN-γ，而Th 2细胞因子很少或没有。GM DC不诱导T细胞极化，尽管在活化后产生大量IL-12 p70。在体内施用DC后观察到类似的T细胞活化模式。这些数据表明，IL-12 p70的生产单独，虽然必要的Th 1分化，是不足以诱导Th 1反应。这些研究对基于DC的疫苗在癌症和其他临床疾病的免疫治疗中的使用具有意义。
Dendritic cells (DCs) activate T cells and regulate their differentiation into T helper cell type 1 (Th1) and/or Th2 cells. To identify DCs with differing abilities to direct Th1/Th2 cell differentiation, we cultured mouse bone marrow progenitors in granulocyte macrophage-colony stimulating factor (GM), GM + interleukin (IL)-4, or GM + IL-15 and generated three distinct DC populations. The GM + IL-4 DCs expressed high levels of CD80/ CD86 and major histocompatibility complex (MHC) class II and produced low levels of IL-12p70. GM and GM + IL-15 DCs expressed low levels of CD80/CD86 and MHC class II. The GM + IL-15 DCs produced high levels of IL-12p70 and interferon (IFN)-gamma, whereas GM DCs produced only high levels of IL-12p70. Naive T cells stimulated with GM + IL-4 DCs secreted high levels of 'IL-4 and IL-5 in addition to IFN-gamma. In contrast, the GM + IL-15 DCs induced higher IFN-gamma production by T cells with little or no Th2 cytokines. GM DCs did not induce T cell polarization, despite producing large amounts of IL-12p70 following activation. A similar pattern of T cell activation was observed after in vivo administration of DCs. These data suggest that IL-12p70 production alone, although necessary for Th1 differentiation, is not sufficient to induce Th1 responses. These studies have implications for the use of DC-based vaccines in immunotherapy of cancer and other clinical conditions.