Mishima H, Hojo M, Watanabe A, Hamid Q A, Martin J G
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, and the Respiratory Health Network of Centres of Excellence, Montreal, Quebec, Canada.
Am J Respir Crit Care Med. 1998 Dec;158(6):1863-70. doi: 10.1164/ajrccm.158.6.9709123.
Airway hyperresponsiveness to inhalational challenge with methacholine (MCh) develops by 32 h after allergen challenge of actively sensitized BN rats. To test the hypothesis that CD4+ T cells mediate allergen-induced hyperresponsiveness independent of IgE-mediated mechanisms, we administered CD4+ T cells, CD8+ T cells, and a mixture of CD4+ and CD8+ T cells (total T cells) isolated from the cervical lymph nodes of rats sensitized with ovalbumin (OA) to naive BN rats that underwent aerosol challenge with either OA or bovine serum albumin (BSA) 2 d later. Responsiveness to MCh was measured 2 d before transfer of T cells and 32 h after challenge with OA or BSA. Airway responsiveness increased significantly in recipients of CD4+ T cells after OA challenge, but not in any other of the treatment groups. Analysis of bronchoalveolar lavage (BAL) cells for major basic protein expression by immunostaining showed eosinophilia in OA-challenged CD4+ and total T-cell recipients. Cells retrieved by bronchoalveolar lavage showed increased expression of IL-5 mRNA (in situ hybridization) in CD4+ T cell recipients after OA challenge compared with other groups. Interferon-gamma mRNA was expressed to the greatest extent in CD8+ recipients, but it was elevated in both OA- and BSA-challenged animals. We conclude that CD4+ T cells can induce airway hyperresponsiveness after inhalational challenge with allergen and this is associated with IL-5 production and eosinophilia. CD8+ T cells may have a negative regulatory effect on responsiveness, possibly mediated by interferon-gamma.
在用变应原攻击主动致敏的BN大鼠后32小时，气道对吸入乙酰甲胆碱（MCh）激发的高反应性出现。为了验证CD4⁺ T细胞介导变应原诱导的高反应性且独立于IgE介导机制这一假说，我们将从用卵清蛋白（OA）致敏的大鼠颈淋巴结分离出的CD4⁺ T细胞、CD8⁺ T细胞以及CD4⁺和CD8⁺ T细胞的混合物（总T细胞）给予未致敏的BN大鼠，2天后这些大鼠接受OA或牛血清白蛋白（BSA）的气雾剂激发。在T细胞转移前2天以及用OA或BSA激发后32小时测量对MCh的反应性。OA激发后，接受CD4⁺ T细胞的受体气道反应性显著增加，但在任何其他治疗组中均未增加。通过免疫染色分析支气管肺泡灌洗（BAL）细胞的主要碱性蛋白表达，结果显示在接受OA激发的CD4⁺和总T细胞受体中有嗜酸性粒细胞增多。与其他组相比，OA激发后，支气管肺泡灌洗回收的细胞在CD4⁺ T细胞受体中显示IL - 5 mRNA表达增加（原位杂交）。干扰素 - γ mRNA在CD8⁺受体中表达程度最高，但在接受OA和BSA激发的动物中均升高。我们得出结论，CD4⁺ T细胞在吸入变应原激发后可诱导气道高反应性，这与IL - 5产生和嗜酸性粒细胞增多有关。CD8⁺ T细胞可能对反应性有负调节作用，可能由干扰素 - γ介导。
