Functional plasticity of human respiratory tract dendritic cells:: GM-CSF enhances TH2 development
Functional plasticity of human respiratory tract dendritic cells:: GM-CSF enhances TH2 development
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DOI：
10.1016/j.jaci.2005.08.002
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发表时间：
2005-11-01
影响因子：
14.2
通讯作者：
Hawrylowicz, C
中科院分区：
文献类型：
--
作者：
Faith, A;McDonald, J;Hawrylowicz, C
背景：人呼吸道粘膜内的树突状细胞（RTDC）被认为可以启动对外源抗原的免疫应答。目的：比较RTDCs与外周血树突状细胞（PBDCs）在表型、细胞因子产生、活化T细胞应答能力以及暴露于多效细胞因子GM-CSE的影响方面的差异。分别从非特异性鼻炎患者的鼻甲和健康人的外周血中纯化CD 1a（+）RTDC和CD 1c（+）PBDC。在一些实验中，比较了来自鼻炎患者的匹配的CD 1c（+）RTDC和PBDC。流式细胞仪检测DC表型，流式细胞仪检测细胞因子的产生。结果：RTDCs和PBDCs均表现为未成熟表型，但RTDCs表达较低水平的MHC Ⅱ类抗原。CD 40在PBDC上而不是RTDC上的交联诱导IL-12 p70的产生。在混合淋巴细胞培养中，RTDC诱导T（H）1/T（H）2谱，而PBDC诱导T（H）1谱。RTDC暴露于GM-CSF诱导混合淋巴细胞培养物中的T（H）2应答模式。结论：本报告强调了研究组织来源的原代DC的重要性，证明了RTDC的功能可塑性，并暗示GM-CSF在增强RTDC在气道中启动T（H）2反应的潜力中起作用。
Background: Dendritic cells within the human respiratory mucosa (RTDCs) are proposed to initiate immune responses to foreign antigens. Their capacity to polarize T-cell responses, however, has not been investigated.Objective: To compare RTDCs with peripheral blood dendritic cells (PBDCs) with regard to phenotype, cytokine production, capacity to polarize T-cell responses, and effects of exposure to the pleiotropic cytokine, GM-CSE.Methods: CD1a(+) RTDCs and CD1c(+) PBDCs were purified from nasal turbinates of patients with nonatopic rhinitis and peripheral blood of healthy individuals, respectively. In some experiments, matched CD1c(+) RTDCs and PBDCs from patients with rhinitis were compared. The phenotype of DC was examined by flow cytometry and cytokine production by cytometric bead array. DCs were cocultured with allogeneic naive CD4(+) T cells, and cytokine production was determined by immunophenotyping, cytometric bead array, and ELISA.Results: Both RTDCs and PBDCs exhibited an immature phenotype, but RTDCs expressed lower levels of MHC class II antigen. Cross-linking of CD40 on PBDCs, but not RTDCs, induced production of IL-12p70. In mixed lymphocyte cultures, RTDCs induced a T(H)1/T(H)2 profile, whereas PBDCs induced a T(H)1 profile. Exposure of RTDCs to GM-CSF induced a T(H)2 pattern of response in the mixed lymphocyte cultures. In contrast, exposure of PBDCs to GM-CSF promoted a T(H)1 response.Conclusion: This report emphasizes the importance of studying tissue-derived primary DCs, demonstrates functional plasticity of RTDCs, and implicates GM-CSF in amplifying the potential of RTDCs to initiate T(H)2 responses in the airways.