Dendritic cell modulation by mast cells controls the Th1/Th2 balance in responding T cells
Dendritic cell modulation by mast cells controls the Th1/Th2 balance in responding T cells
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DOI：
10.4049/jimmunol.177.6.3577
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发表时间：
2006-09-15
影响因子：
4.4
通讯作者：
Segal, David M.
中科院分区：
文献类型：
--
作者：
Mazzoni, Alessandra;Siraganian, Reuben P.;Segal, David M.
病原体激活的人树突状细胞（DC）分泌的细胞因子在体外受到组胺（肥大细胞颗粒的主要成分）的强烈调节，最终调节DC极化幼稚T细胞的能力。由于DC和肥大细胞位于紧密接近的外周隔室，我们假设肥大细胞的产品会影响DC的成熟，因此Th平衡的免疫反应在体内。在这项研究中，我们表明，特定的肥大细胞脱粒刺激，给予s.c.在具有Ag和佐剂的小鼠中，产生增殖为Ag的效应T细胞，但与在不存在肥大细胞刺激物的情况下致敏的对照T细胞相比，其分泌显著降低水平的IFN-γ和增加量的IL-4。与来自缺乏脱粒刺激的小鼠的DC相比，在存在脱粒刺激的情况下用Ag和佐剂免疫也导致DC在引流淋巴结中的积累，所述引流淋巴结具有降低的诱导Ag特异性Th 1细胞的能力。因此，通过作用于炎症部位的DC，肥大细胞在体内确定Ag特异性T细胞应答的极性中起关键作用。
The cytokines secreted by pathogen-activated human dendritic cells (DC) are strongly regulated in vitro by histamine, a major component of mast cell granules, ultimately modulating the capacity of the DC to polarize naive T cells. Because DC and mast cells are located in-close proximity in peripheral compartments, we hypothesized that mast cell products would influence the maturation of DC and hence the Th balance of an immune response in vivo. In this study, we show that specific mast cell degranulation stimuli, given s.c. in mice with Ag and adjuvant, produce effector T cells that proliferate to Ag but secrete dramatically reduced levels of IFN-gamma and increased amounts of IL-4 compared with control T cells primed in the absence of a mast cell stimulus. Immunization with Ag and adjuvant in the presence of a degranulation stimulus also resulted in the accumulation of DC in the draining lymph nodes that had reduced capacity to induce Ag-specific Th1 cells, in comparison with DC from mice lacking a degranulation stimulus. Therefore, by acting upon DC at sites of inflammation, mast cells play a critical role in determining the polarity of Ag-specific T cell responses in vivo.