Freshly isolated Peyer's patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells.
Freshly isolated Peyer's patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells.
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DOI：
10.1084/jem.190.2.229
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发表时间：
1999-07-19
期刊：
影响因子：
--
通讯作者：
Kelsall BL
中科院分区：
文献类型：
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作者：
Iwasaki A;Kelsall BL
口服施用的抗原通常产生与全身注射的免疫应答不同的免疫应答。抗原呈递细胞在决定粘膜与全身部位诱导的T辅助细胞应答类型中的作用尚不清楚。在这里，我们研究树突状细胞（DC）新鲜分离派尔集合淋巴结（PP）和脾脏（SP）之间的表型和功能差异。CD 11 c + DC群体的表面表型分析显示，PP DC表达更高水平的主要组织相容性复合物II类分子，但与SP DC相比，共刺激分子和粘附分子的水平相似。比较新鲜分离的、流式细胞术分选的来自PP和SP的98-100%纯CD 11 c + DC群体刺激幼稚T细胞的能力。首先，发现PP DC在刺激同种异体T细胞增殖方面比SP DC强得多。其次，通过使用来自卵清蛋白肽特异性T细胞受体转基因小鼠的幼稚T细胞，发现这些来自PP而不是来自SP的离体DC引发白细胞介素（IL）-4和IL-10（Th 2细胞因子）的产生。此外，与SP DC相比，发现PP DC引发T细胞产生低得多的水平的干扰素（IFN）-γ（Th 1）。在引发培养物中存在针对IL-10的中和抗体显著增强了用PP DC刺激的T细胞的IFN-γ产生。此外，通过CD 40分子刺激新鲜分离的PP DC导致高水平的IL-10分泌，而相同的刺激不诱导SP DC分泌IL-10。这些结果表明，驻留在不同组织中的DC能够诱导不同的免疫应答，这可能与来自这些组织的DC产生的不同细胞因子有关。
Orally administered antigens often generate immune responses that are distinct from those injected systemically. The role of antigen-presenting cells in determining the type of T helper cell response induced at mucosal versus systemic sites is unclear. Here we examine the phenotypic and functional differences between dendritic cells (DCs) freshly isolated from Peyer's patches (PP) and spleen (SP). Surface phenotypic analysis of CD11c+ DC populations revealed that PP DCs expressed higher levels of major histocompatibility complex class II molecules, but similar levels of costimulatory molecules and adhesion molecules compared with SP DCs. Freshly isolated, flow cytometrically sorted 98–100% pure CD11c+ DC populations from PP and SP were compared for their ability to stimulate naive T cells. First, PP DCs were found to be much more potent in stimulating allogeneic T cell proliferation compared with SP DCs. Second, by using naive T cells from ovalbumin peptide–specific T cell receptor transgenic mice, these ex vivo DCs derived from PP, but not from SP, were found to prime for the production of interleukin (IL)-4 and IL-10 (Th2 cytokines). In addition, PP DCs were found to prime T cells for the production of much lower levels of interferon (IFN)-γ (Th1) compared with SP DCs. The presence of neutralizing antibody against IL-10 in the priming culture dramatically enhanced IFN-γ production by T cells stimulated with PP DCs. Furthermore, stimulation of freshly isolated PP DCs via the CD40 molecule resulted in secretion of high levels of IL-10, whereas the same stimulus induced no IL-10 secretion from SP DCs. These results suggest that DCs residing in different tissues are capable of inducing distinct immune responses and that this may be related to the distinct cytokines produced by the DCs from these tissues.