Antigen-sensitized CD4+CD62Llow memory/effector T helper 2 cells can induce airway hyperresponsiveness in an antigen free setting.
Antigen-sensitized CD4+CD62Llow memory/effector T helper 2 cells can induce airway hyperresponsiveness in an antigen free setting.
复制标题
DOI：
10.1186/1465-9921-6-46
复制
发表时间：
2005-05-28
影响因子：
5.8
通讯作者：
Yamamoto K
中科院分区：
文献类型：
--
作者：
Nakagome K;Dohi M;Okunishi K;To Y;Sato A;Komagata Y;Nagatani K;Tanaka R;Yamamoto K
气道高反应性（AHR）是哮喘最显著的特征之一，然而其确切的诱导机制尚未完全阐明。我们以前报道，在过敏性气道炎症小鼠模型中，仅全身抗原致敏在嗜酸性粒细胞气道炎症发生之前直接诱导AHR，这表明抗原特异性全身免疫应答本身在诱导AHR中起关键作用。在本研究中，我们通过细胞转移实验验证了这种可能性，然后分析了这一过程中所必需的细胞来源。用卵清蛋白（OVA）免疫BALB/c小鼠2次。从小鼠获得脾细胞并转移到未处理小鼠中。4天后，对AHR进行评估。我们进行了支气管肺泡灌洗（BAL），以分析炎症和细胞因子在肺中的产生。进行荧光和免疫组织化学研究以鉴定T细胞在受体的肺或肠中的募集和增殖。为了确定必需表型，脾细胞通过抗体包被的微珠柱纯化，具有阴性或阳性选择，并转移。然后，对AHR进行了评估。从OVA致敏小鼠获得的脾细胞的转移诱导了中度，但显着的，AHR没有气道抗原激发在没有气道嗜酸性粒细胞增多症的幼稚小鼠。辅助性T细胞（Th）1诱导抗原（含完全弗氏佐剂的卵清蛋白）免疫不诱导AHR。转移的细胞分布在器官中，并且细胞在无抗原环境中在肺中增殖至少三天。这种转移诱导的AHR持续了一周。BALF中IL-4和IL-5的水平在转移小鼠中升高。免疫球蛋白E不参与这种转移诱导的AHR。在体外极化的CD 4 + Th 2细胞，而不是Th 1细胞的转移，诱导AHR。我们最终阐明了CD 4 + CD 62 Llow记忆/效应T细胞在肺中募集并增殖，从而诱导AHR。这些结果表明，抗原致敏的记忆/效应Th 2细胞本身发挥了重要的作用，诱导基础AHR在无抗原，嗜酸性粒细胞的独立设置。因此，调节CD 4 + T细胞介导的免疫应答本身可能是过敏性哮喘的关键治疗靶点。
Airway hyperresponsiveness (AHR) is one of the most prominent features of asthma, however, precise mechanisms for its induction have not been fully elucidated. We previously reported that systemic antigen sensitization alone directly induces AHR before development of eosinophilic airway inflammation in a mouse model of allergic airway inflammation, which suggests a critical role of antigen-specific systemic immune response itself in the induction of AHR. In the present study, we examined this possibility by cell transfer experiment, and then analyzed which cell source was essential for this process. BALB/c mice were immunized with ovalbumin (OVA) twice. Spleen cells were obtained from the mice and were transferred in naive mice. Four days later, AHR was assessed. We carried out bronchoalveolar lavage (BAL) to analyze inflammation and cytokine production in the lung. Fluorescence and immunohistochemical studies were performed to identify T cells recruiting and proliferating in the lung or in the gut of the recipient. To determine the essential phenotype, spleen cells were column purified by antibody-coated microbeads with negative or positive selection, and transferred. Then, AHR was assessed. Transfer of spleen cells obtained from OVA-sensitized mice induced a moderate, but significant, AHR without airway antigen challenge in naive mice without airway eosinophilia. Immunization with T helper (Th) 1 elicited antigen (OVA with complete Freund's adjuvant) did not induce the AHR. Transferred cells distributed among organs, and the cells proliferated in an antigen free setting for at least three days in the lung. This transfer-induced AHR persisted for one week. Interleukin-4 and 5 in the BAL fluid increased in the transferred mice. Immunoglobulin E was not involved in this transfer-induced AHR. Transfer of in vitro polarized CD4+ Th2 cells, but not Th1 cells, induced AHR. We finally clarified that CD4+CD62Llow memory/effector T cells recruited in the lung and proliferated, thus induced AHR. These results suggest that antigen-sensitized memory/effector Th2 cells themselves play an important role for induction of basal AHR in an antigen free, eosinophil-independent setting. Therefore, regulation of CD4+ T cell-mediated immune response itself could be a critical therapeutic target for allergic asthma.
登录
查看更多内容
DOI：
10.1159/000235204
发表时间：
1990-06-01
期刊：
INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY
影响因子：
--
作者：
DOHI, M;OKUDAIRA, H;MIYAMOTO, T
通讯作者：
MIYAMOTO, T
DOI：
10.1164/ajrccm.156.3.9606031
发表时间：
1997-09-01
影响因子：
24.7
作者：
Hamelmann, E;Schwarze, J;Gelfand, EW
通讯作者：
Gelfand, EW
影响因子：
4.4
作者：
Byersdorfer, CA;Chaplin, DD
通讯作者：
Chaplin, DD
DOI：
10.1164/ajrccm.162.6.9908097
发表时间：
2000-12-01
影响因子：
24.7
作者：
Dohi, M;Hasegawa, T;Marshall, BC
通讯作者：
Marshall, BC
DOI：
10.1152/ajplung.00324.2001
发表时间：
2002-07-01
影响因子：
4.9
作者：
Albertine, KH;Wang, L;McIntyre, TM
通讯作者：
McIntyre, TM