Mucosal CD8α+ DC, with a plasmacytoid phenotype, induce differentiation and support function of T cells with regulatory properties
Mucosal CD8α+ DC, with a plasmacytoid phenotype, induce differentiation and support function of T cells with regulatory properties
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DOI：
10.1046/j.1365-2567.2003.01606.x
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发表时间：
2003-04-01
期刊：
影响因子：
6.4
通讯作者：
Viney, JL
中科院分区：
文献类型：
--
作者：
Bilsborough, J;George, TC;Viney, JL
未成熟的脾树突状细胞(DC)对初始T细胞的重复刺激可导致具有调节特性的T细胞系的分化。在本研究中，我们在粘膜中发现了一群DC，它们表现为浆细胞样表型，在含有某些胞嘧啶-磷酸-鸟苷(CpG)基序的寡脱氧核苷酸刺激下分泌干扰素-α(IFN-α)，并能将初始T细胞分化为具有调节特性的细胞。虽然这些DC似乎存在于脾和肠系膜淋巴结(MLN)中，但只有来自MLN(而不是脾)的CpG成熟DC能够将原始T细胞分化为具有调节特性的T调节性1样细胞。这些DC的活性未能维持强劲的T细胞增殖，从而增强了CD4(+)CD25(+)T调节细胞的抑制效果。这些DC是Peyer‘s斑块(PP)中主要的CD8α(+)DC群体。鉴于它们在粘膜组织中的显著存在，我们认为这些DC可能通过在肠道等高抗原性刺激部位引发调节细胞抑制功能和支持T辅助细胞增殖而为肠道内的动态平衡调节提供机制基础。
Repetitive stimulation of naive T cells by immature splenic dendritic cells (DC) can result in the differentiation of T-cell lines with regulatory properties. In the present study we identified a population of DC in the mucosae that exhibit the plasmacytoid phenotype, secrete interferon-alpha (IFN-alpha) following stimulation with oligodeoxynucleotides containing certain cytosine-phosphate-guanosine (CpG) motifs and can differentiate naive T cells into cells that exhibit regulatory properties. Although these DC appear to be present in both spleen and mesenteric lymph nodes (MLN), only CpG-matured DC from the MLN (but not the spleen) were able to differentiate naive T cells into T regulatory 1-like cells with regulatory properties. The activity of these DC failed to sustain robust T-cell proliferation and thereby enhanced the suppressive efficacy of CD4(+) CD25(+) T regulatory cells. These DC are the major CD8alpha(+) DC population in the Peyer's patches (PP). Given their significant presence in mucosal tissue, we propose that these DC may provide a mechanistic basis for the homeostatic regulation in the gut by eliciting regulatory cell suppressor function and poorly supporting T helper cell proliferation at a site of high antigenic stimulation like the intestine.