Research on experimental allergic mouse engrafted with human lymphocytes from allergic diseases

目的：粉尘螨抗原（Dermatophagoides farinae，Df，mite antigen）致敏是小儿哮喘的主要致敏因素。活动期哮喘患者外周血淋巴细胞在Df抗原刺激下产生的干扰素-γ（IFN-γ）减少，白细胞介素4（IL-4）增加。相反，缓解期患者的淋巴细胞能够通过调节辅助性T淋巴细胞的失衡产生高TNF-γ和低IL-4。从缓解期支气管哮喘患者和健康人中获得的T细胞克隆（TCC）进行了比较，关于细胞因子的产生。方法：TCC通过体外重复刺激Df抗原产生。结果：Df特异性TCC在缓解期患者中的检出率（5-10%）高于正常人（1-2%）。来自缓解期患者的大多数TCC仅产生IL-4（Th 2），少数克隆沿着IL-4合成大量IFN-γ（Tho）。相反，健康人TCC产生的IFN-γ和11- 4的量较低。讨论：哮喘缓解期患者的循环中仍有比健康人更多的Df特异性TCC，尽管缓解期患者明显没有疾病体征。处于缓解期的患者中的TCC含有可加剧过敏反应的Th 2细胞，其可被少量产生高滴度IFN-γ的ThO细胞抑制。将这些TCC转移到严重联合免疫缺陷（SCID）小鼠中可能允许分析人类过敏性疾病的缓解和复发。

Objective : The majority of asthmatic patients in children is sensitized with Dermatophagoides farinae (Df, mite antigen. Peripheral blood lymphocytes from active patients with asthma produced decreased interferon-gamma (IFN-gamma) and increased interleukin 4 (IL-4) upon stimulation with Df antigen. In contrast, patients in remission have lymphocytes capable of producing high TFN-y and low 1L-4 by modulating the imbalance of helper T lymphocytes. T cell clones (TCC) obtained from patients with bronchial asthma in remission and from healthy individuals were compared with respect to cytokine production.Methods : TCC were generated by in vitro repetitive stimulation with Df antigen. Interferon-y (IFN-gamma) and interleukin 4 (IL-4) production by these TCC was measured by enzyme-linked immunoassay.Results : Df-specific TCC were more frequently (5-10%) obtained from patients in remission than from healthy individuals (1-2%). Most TCC from patients in remission produced IL-4 alone (Th2) with a few clones synthesizing high amount of IFN-gamma along with IL-4 (Tho). In contrast, TCC from healthy individuals generated low amount of IFN-gamma and 11-4.Discussion : Asthmatic patients in remission still have more Df-specific TCC than in healthy individuals in their circulation, although patients in remission showed apparently no sighs of disease. The TCC in patients in remission contains Th2 cells that could exacerbate allergic reaction, which may be suppressed by small numbers of ThO cells producing high titers of IFN-gamma. Transfer of these TCC into severe combined immunodeficiency (SCID) mice might allow the analysis of human allergic disease in terms of remission and recurrence.