Watanabe A, Mishima H, Renzi P M, Xu L J, Hamid Q, Martin J G
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
J Clin Invest. 1995 Sep;96(3):1303-10. doi: 10.1172/JCI118165.
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.
活化的CD4+辅助性T细胞已在哮喘气道中得到证实,并被推测在引发过敏性炎症中起核心作用;但其参与的直接证据似乎尚缺。我们假设CD4+ T细胞有潜力诱导对抗原攻击的过敏反应,并在过敏性支气管收缩模型——棕色挪威大鼠中,采用过继转移方法对这一假设进行了验证。动物被主动致敏于卵清蛋白(OVA)或牛血清白蛋白(BSA),并用作T细胞供体。从致敏供体的颈淋巴结中分离出W3/25(CD4)+或OX8(CD8)+ T细胞,并转移至未致敏的BN大鼠。过继转移后2天,受体大鼠通过吸入OVA进行攻击,并研究肺阻力(RL)、支气管肺泡灌洗(BAL)细胞以及抗原特异性IgE血清水平的变化。OVA攻击后,用OVA致敏的W3/25+ T细胞的受体在整个8小时观察期内RL持续升高,并有显著的支气管肺泡灌洗嗜酸性粒细胞增多,这通过使用抗主要碱性蛋白单克隆抗体的免疫细胞化学检测到。用BSA致敏的W3/25+ T细胞或用OVA致敏的OX8+ T细胞的受体对吸入的OVA无反应。过继转移后,在任何受体大鼠中,通过ELISA或皮肤试验均未检测到OVA特异性免疫球蛋白E。总之,在棕色挪威大鼠中,抗原特异性W3/25+ T细胞成功转移了抗原诱导的气道支气管收缩和嗜酸性粒细胞增多。这些反应依赖于抗原致敏的W3/25+ T细胞,且似乎独立于IgE介导的肥大细胞活化。本研究为该实验模型中过敏性气道反应的T细胞介导免疫机制提供了明确证据。