Mouse lung CD103+ and CD11bhigh dendritic cells preferentially induce distinct CD4+ T-cell responses.
Mouse lung CD103+ and CD11bhigh dendritic cells preferentially induce distinct CD4+ T-cell responses.
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DOI：
10.1165/rcmb.2011-0070oc
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发表时间：
2012-02-01
影响因子：
6.4
通讯作者：
Chida, Kingo
中科院分区：
文献类型：
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作者：
Furuhashi, Kazuki;Suda, Takafumi;Chida, Kingo
近来发现小鼠肺树突状细胞(LDC)有两个主要亚群：CD103(+)、CD11b(低或阴性)(CD103(+))和CD103(-)、CD11b(高)。尽管一些研究已经证明了它们之间的功能差异，但尚不清楚这些亚群是否会诱导不同的T辅助(Th)细胞反应。本研究旨在探讨CD103(+)和CD11b(高)最不发达国家是否优先产生不同的Th应答。用正常BALB/c小鼠的CD103(+)或CD11b(高)小鼠的CD103(+)或CD11b(高)小鼠的CD103(+)或CD11b(高)LDC免疫幼稚的DO11.10(+)T细胞。重新刺激预置的CD4(+)T细胞，并检测其细胞因子的分泌。同时检测细胞内细胞因子的表达和趋化因子受体的mRNA水平。我们发现，CD103(+)LDC诱导的CD4(+)T细胞分泌显著更多的干扰素-γ和IL-17A，而CD11b(高)LDC诱导的CD4(+)T细胞显著释放更高水平的IL-4、IL-6和IL-10。细胞内细胞因子分析显示，CD103(+)LDC诱导的CD4(+)T细胞产生干扰素-γ和IL-17A的频率较高，而CD11b(高)LDC诱导CD4(+)T细胞产生IL-4和IL-10的效率更高。CD103(+)DC诱导的CD4(+)T细胞优先表达CXCR3和CCR5的mRNA水平显著高于CD103(+)DC。主要在Th2细胞中表达的CXCR4和CCR4的mRNA水平在CD11b(高)LDC组显著高于CD11b(高)组。这些数据表明，小鼠CD103(+)LDC主要激发Th1和Th17反应，而CD11b(高)LDC在稳态下主要激发Th2反应。
Mouse lung dendritic cells (LDCs) have been recently shown to contain two major subpopulations: CD103(+) CD11b(low or negative) (CD103(+) LDCs) and CD103(-) CD11b(high) LDCs (CD11b(high) LDCs). Although several studies have demonstrated functional differences between them, it is unclear whether the subpopulations induce distinct T helper (Th) cell responses. The present study was conducted to examine whether CD103(+) and CD11b(high) LDCs preferentially generate different Th responses. Naive DO11.10 CD4(+) T cells were primed with CD103(+) or CD11b(high) LDCs obtained from normal BALB/c mice. The primed CD4(+) T cells were restimulated, and their cytokine secretions were assessed. The expression of intracellular cytokines and the mRNA levels of chemokine receptors were also measured. We found that the CD4(+) T cells primed with CD103(+) LDCs secreted significantly larger amounts of IFN-gamma and IL-17A, whereas those primed with CD11b(high) LDCs released significantly higher levels of IL-4, IL-6, and IL-10. Intracellular cytokine assay showed that CD103(+) LDCs induced greater frequencies of CD4(+) T cells producing IFN-gamma and IL-17A, whereas CD11b(high) LDCs were more efficient at inducing CD4(+) T cells producing IL-4 and IL-10. The mRNA levels of CXCR3 and CCR5, which are expressed preferentially in Th1 cells, were significantly higher in CD4(+) T cells primed with CD103(+) LDCs. The mRNA levels of CXCR4 and CCR4, which are expressed primarily in Th2 cells, were significantly greater in those primed with CD11b(high) LDCs. These data suggest that mouse CD103(+) LDCs predominantly elicit Th1 and Th17 responses, whereas CD11b(high) LDCs primarily provoke a Th2 response under the steady state.