Nagatani Katsuya, Dohi Makoto, To Yasuo, Tanaka Ryoichi, Okunishi Katsuhide, Nakagome Kazuyuki, Sagawa Kayo, Tanno Yudo, Komagata Yoshinori, Yamamoto Kazuhiko
Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
J Immunol. 2006 Feb 1;176(3):1481-9. doi: 10.4049/jimmunol.176.3.1481.
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 of 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.
喂食抗原后可诱导外周耐受，这被称为口服耐受。我们在本研究中证明，口服卵清蛋白（OVA）可在小鼠哮喘实验模型中诱导耐受，并研究了在这种口服耐受传递过程中哪些细胞作为调节性细胞发挥作用。在喂食OVA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和嗜酸性粒细胞趋化因子的mRNA水平均显著低于未喂食的小鼠。肺组织的组织学检查显示，喂食OVA的小鼠支气管周围区域炎症细胞的积聚受到抑制。在首次免疫后或首次与第二次免疫之间进行喂食可抑制这些结果，而在气道抗原攻击前立即喂食则没有这种效果。通过注射喂食OVA小鼠的全脾细胞，成功地将喂食OVA小鼠疾病的抑制作用进行了传递。当从脾细胞中去除CD11c+树突状细胞（DCs）时，这种抑制作用的传递完全被消除。单独注射从喂食OVA小鼠中纯化的脾DCs可传递抑制作用，而注射体外与OVA共培养的未接触过抗原小鼠的脾DCs则不能。这些数据表明，在这个小鼠哮喘实验模型中，不仅CD4+ T细胞，而且由抗原喂食诱导的CD11c+ DCs对于口服耐受的主动传递都很重要。
