Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ T cells in brown Norway rats.

Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ T cells in brown Norway rats.
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在棕色挪威大鼠中用抗原引发的 CD4 T 细胞而非 CD8 T 细胞转移过敏性气道反应。

DOI:
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发表时间:
1995
影响因子:
15.9
通讯作者:
James G. Martin
James G. Martin
中科院分区:
医学1区
文献类型:
--
作者:
Azuma Watanabe;H. Mishima;Paolo M. Renzi;Li;Qutayba Hamid;James G. Martin

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活化的CD 4+辅助性T细胞已在哮喘气道中被证实,并被假定在引发过敏性炎症中发挥核心作用;似乎缺乏其参与的直接证据。我们假设,CD 4 + T细胞有可能诱导过敏反应抗原的挑战,并测试这一假设在过敏性支气管收缩模型,布朗挪威大鼠,采用过继转移的方法。动物主动致敏卵清蛋白(OVA)或BSA,并用作T细胞的供体。从致敏供体的颈部淋巴结分离W3/25(CD 4)+或OX 8(CD 8)+ T细胞,并转移至幼稚BN大鼠。2天后过继转移受体大鼠的挑战,通过卵蛋白吸入,肺阻力(RL),支气管肺泡灌洗(BAL)细胞,和血清抗原特异性IgE水平的变化进行了研究。在OVA激发后,OVA致敏的W3/25+ T细胞的受体在整个8小时的观察期内表现出RL的持续增加,并且具有显著的支气管肺泡灌洗液嗜酸性粒细胞增多,这是通过使用抗主要碱性蛋白mAb的免疫细胞化学检测到的。BSA致敏的W3/25+ T细胞或OVA致敏的OX 8 + T细胞的受体对吸入的OVA没有应答。OVA特异性免疫球蛋白E在过继转移后的任何受体大鼠中通过ELISA或皮肤试验检测不到。总之,在Brown Norway大鼠中,抗原诱导的气道支气管收缩和嗜酸性粒细胞增多被抗原特异性W3/25+ T细胞成功转移。这些反应依赖于抗原引发的W3/25+ T细胞,似乎是独立的IgE介导的肥大细胞活化。本研究为T细胞介导的免疫机制在该实验模型中的过敏性气道反应提供了明确的证据。
Activated CD4+ helper T cells have been demonstrated in asthmatic airways and postulated to play a central role in eliciting allergic inflammation; direct evidence of their involvement seems to be lacking. We hypothesized that CD4+ T cells have the potential to induce allergic responses to antigen challenge, and tested this hypothesis in a model of allergic bronchoconstriction, the Brown Norway rat, using the approach of adoptive transfer. Animals were actively sensitized to either ovalbumin (OVA) or BSA and were used as donors of T cells. W3/25(CD4)+ or OX8(CD8)+ T cells were isolated from the cervical lymph nodes of sensitized donors and transferred to naive BN rats. 2 d after adoptive transfer recipient rats were challenged by OVA inhalation, and changes in lung resistance (RL), bronchoalveolar lavage (BAL) cells, and serum levels of antigen-specific IgE were studied. After OVA challenge recipients of OVA-primed W3/25+ T cells exhibited sustained increases in RL throughout the entire 8-h observation period and had significant bronchoalveolar lavage eosinophilia, which was detected by immunocytochemistry using an antimajor basic protein mAb. Recipients of BSA-primed W3/25+ T cells or OVA-primed OX8+ T cells failed to respond to inhaled OVA. OVA-specific immunoglobulin E was undetectable by ELISA or skin testing in any of the recipient rats after adoptive transfer. In conclusion, antigen-induced airway bronchoconstriction and eosinophilia were successfully transferred by antigen-specific W3/25+ T cells in Brown Norway rats. These responses were dependent on antigen-primed W3/25+ T cells and appeared to be independent of IgE-mediated mast cell activation. This study provides clear evidence for T cell mediated immune mechanisms in allergic airway responses in this experimental model.
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