Frew A, Chang J H, Chan H, Quirce S, Noertjojo K, Keown P, Chan-Yeung M
University Medicine, University of Southampton, United Kingdom.
J Allergy Clin Immunol. 1998 Jun;101(6 Pt 1):841-7. doi: 10.1016/S0091-6749(98)70313-6.
T cells are known to play a major role in the pathogenesis of atopic allergic asthma, but it is less clear whether they are involved in occupational asthma caused by low molecular weight chemicals such as plicatic acid.
We sought to determine whether peripheral blood T cells from patients with western red cedar asthma (WRCA) recognize plicatic acid (PA) conjugated to human serum albumin (HSA) as judged by proliferation or cytokine production and to analyze the response to PA inhalation with flow cytometry.
Significant proliferative responses to PA-HSA were observed in eight of 33 patients with WRCA, none of 10 exposed nonasthmatic cedar workers, and one of 18 nonasthmatic control subjects. Two of 25 patients with WRCA also showed proliferative responses to unconjugated PA. All the WRCA responders were either currently exposed to cedar or had ceased exposure within the preceding 2 years. None of the four patients receiving oral steroids responded, but inhaled steroids did not seem to influence responsiveness. No correlations were found between the maximum stimulation response and any of the current FEV1 values, the current PC20 methacholine values, or the magnitude of the late asthmatic response to PA. Peripheral blood T-cell subset proportions and their degree of activation were similar in patients with WRCA and exposed control subjects. There was no change in T-cell phenotypes or their activation markers after PA inhalation challenge. In vitro, PA-HSA stimulation did not affect subset ratios but led to release of small amounts of IL-5 and IFN-gamma, with no detectable increase in IL-4.
PA-HSA-specific T lymphocytes seem to be present in small numbers in the peripheral blood of patients with WRCA and may respond to antigenic exposure by producing IFN-gamma and IL-5. However, the proportion of responding cells would appear to be lower than in comparable studies of atopic asthma.
已知T细胞在特应性过敏性哮喘的发病机制中起主要作用，但它们是否参与由低分子量化学物质如扁柏酸引起的职业性哮喘尚不清楚。
我们试图确定西部红雪松哮喘（WRCA）患者的外周血T细胞是否通过增殖或细胞因子产生来识别与人血清白蛋白（HSA）结合的扁柏酸（PA），并通过流式细胞术分析对PA吸入的反应。
33例WRCA患者中有8例对PA-HSA有显著的增殖反应，10例暴露的非哮喘雪松工人中无1例有反应，18例非哮喘对照受试者中有1例有反应。25例WRCA患者中有2例对未结合的PA也有增殖反应。所有有反应的WRCA患者要么目前接触雪松，要么在之前2年内停止接触。4例接受口服类固醇治疗的患者均无反应，但吸入类固醇似乎不影响反应性。最大刺激反应与当前任何FEV1值、当前PC20乙酰甲胆碱值或对PA的迟发性哮喘反应程度之间均未发现相关性。WRCA患者和暴露的对照受试者外周血T细胞亚群比例及其活化程度相似。PA吸入激发后T细胞表型及其活化标志物无变化。在体外，PA-HSA刺激不影响亚群比例，但导致少量IL-5和IFN-γ释放，IL-4未检测到增加。
PA-HSA特异性T淋巴细胞似乎少量存在于WRCA患者的外周血中，可能通过产生IFN-γ和IL-5对抗抗原暴露。然而，反应细胞的比例似乎低于特应性哮喘的类似研究。
