Splenic dendritic cells induced by oral antigen administration are important for the transfer of oral tolerance in an experimental model of asthma

Splenic dendritic cells induced by oral antigen administration are important for the transfer of oral tolerance in an experimental model of asthma
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DOI:
10.4049/jimmunol.176.3.1481
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发表时间:
2006-02-01
影响因子:
4.4
通讯作者:
Yamamoto, K
Yamamoto, K
中科院分区:
医学2区
文献类型:
--
作者:
Nagatani, K;Dohi, M;Yamamoto, K

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在喂饲Ag后可诱导外周耐受,这被称为口服耐受。我们在这项研究中证明,口服卵蛋白在小鼠哮喘实验模型中诱导了耐受性,并研究了哪些细胞在这种口服耐受性的转移中充当调节细胞。在OVA喂养的小鼠中,支气管肺泡灌洗液中嗜酸性粒细胞的百分比、血清IgE水平、气道高反应性以及IL-13和eotaxin的mRNA水平显著低于未喂养的小鼠。肺组织的组织学检查显示,OVA喂养小鼠支气管周围区域的炎性细胞积聚受到抑制。第一次免疫后或第一次和第二次免疫之间的喂养抑制了这些发现,而在气道Ag激发前喂养没有。通过注射饲喂OVA的小鼠的整个脾细胞,成功地转移了饲喂OVA的小鼠中的疾病抑制。当从脾细胞中去除CD 11 c(+)树突状细胞(DCs)时,这种抑制的转移被完全消除。注射从单独的OVA喂养的小鼠纯化的脾DC转移抑制,而注射从与OVA在体外共培养的幼稚小鼠的脾DC没有。这些数据表明,不仅CD 4(+)T细胞,而且CD 11 c(+)DC诱导的银喂养是重要的主动转移口服耐受在这个小鼠实验模型的哮喘。
Peripheral tolerance can be induced after the feeding of Ag, which is referred to as oral tolerance. We demonstrated in this study that the oral administration of OVA induced tolerance in an experimental model of asthma in mice, and investigated which cells function as the regulatory cells in the transfer of this oral tolerance. In OVA-fed mice, the percentage of eosinophils in bronchoalveolar lavage fluid, serum IgE levels, airway hyperresponsiveness, and mRNA levels of IL-13 and eotaxin were significantly lower than found in nonfed mice. Histological examination or lung tissue showed a suppression of the accumulation of inflammatory cells in the peribronchial area of OVA-fed mice. Feeding after the first immunization or between the first and the second immunization suppressed these findings, whereas feeding just before the airway Ag challenge did not. The suppression of disease in OVA-fed mice was successfully transferred by injection of whole spleen cells of OVA-fed mice. When CD11c(+) dendritic cells (DCs) were removed from splenocytes, this transfer of suppression was completely abolished. The injection of splenic DCs purified from OVA-fed mice alone transferred the suppression, whereas the injection of splenic DCs from naive mice that were cocultured with OVA in vitro did not. These data suggest that not only CD4(+) T cells, but also CD11c(+) DCs induced by Ag feeding are important for the active transfer of oral tolerance in this murine experimental model of asthma.