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

过敏性疾病人淋巴细胞移植实验性过敏小鼠的研究

基本信息

批准号：
09670833
负责人：
KAWANO Yutaka
金额：
$ 1.54万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670833/
关键词：
Bronchial asthma remission mite antigen T cell clone interferon-gamma interleukin 4 helper T cell severe combined immunodeficiency mice interleukin4 T細胞クローン重症複合免疫不全(SCID)マウス Th0 Th1 Th2

项目摘要

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.

目的：大多数儿童哮喘患者用粉尘螨(DF，粉尘螨抗原)致敏。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降低，白介素4升高。相比之下，缓解期患者的淋巴细胞能够通过调节辅助性T淋巴细胞的失衡来产生高TFN-Y和低1L-4。比较缓解期哮喘患者和健康人T细胞克隆(TCC)细胞因子的产生情况。方法：采用体外重复刺激DF抗原的方法获得TCC。结果：缓解期患者的DC特异性TCC发生率(5~10%)明显高于健康人(1~2%)。大多数缓解期TCC仅产生IL-4(Th2)，少数克隆与IL-4(Tho)一起合成高水平的干扰素-γ。相反，健康人的TCC产生的干扰素-γ和11-4的量较低。讨论：缓解期哮喘患者的循环中仍有更多的DF特异性TCC，尽管缓解期患者明显没有疾病迹象。缓解期患者的TCC含有Th2细胞，可能会加剧过敏反应，这可能会被少量产生高滴度干扰素-伽马的Tho细胞抑制。将这些TCC转移到严重联合免疫缺陷(SCID)小鼠中，可能会从缓解和复发的角度分析人类过敏性疾病。