Study of the pathogenesis of intrinsic asthma by establishing T cell clones

支气管黏膜慢性嗜酸性粒细胞性炎症在支气管哮喘的病理生理学上已得到公认。T细胞和T细胞因子的作用，特别是IL-5，与嗜酸性粒细胞的局部浸润和激活密切相关。我们已经表明，CD4^+ T细胞在特应性和非特应性（内在）哮喘患者中均观察到IL-5产生的增强。通过活化的T细胞控制IL-5的产生必须是一种有益的方法来管理过敏性疾病的特点是嗜酸性粒细胞炎症。为了明确人类“过敏性”T细胞产生IL-5的确切机制，我们建立了哮喘患者的T细胞克隆，并分析了这些辅助T细胞克隆产生的细胞因子。IL-5的合成需要PKC激活和Ca^<++>内流。转录因子NF-AT和AP-1参与了IL-5基因的转录。人T细胞合成IL-5依赖于内源性产生的IL-2。重组人IL-2在产生IL-5的T细胞克隆中启动IL-5基因转录。一些内源性哮喘患者的PBMC对螨过敏原提取物产生IL-5。从这些患者身上建立的T细胞克隆确实产生了IL-5，以响应螨虫过敏原，这表明螨虫过敏原可能部分负责所谓的“内在”哮喘。

Chronic eosinophilic inflammation of bronchial mucosa has been recognized in the pathophysilology of bronchial asthma. The roles of T cells and T cell cytokines, including especially IL-5, have been strongly implicated in the local infiltration and activation of eosinophils. We have indicated that enhanced IL-5 production by CD4^+ T cells is observed in both atopic and non-atopic (intrinsic) asthmatics. Control of IL-5 production by activated T cells must be a beneficial approach to manage allergic diseases characterized by eosinophilic inflammation. In order to delineate the precise mechanisms of IL-5 production by human "allergic" T cells, we established T cell clones from asthmatic patitents and analyzed cytokine production by those helper T cell clones. Both PKC activation and Ca^<++> influx were required for IL-5 synthesis. The transcription factors, NF-AT and AP-1 were suggested to be involved in IL-5 gene transcription. IL-5 synthesis by human T cells was dependent on endogeneously produced IL-2. Human recombinant IL-2 initiated IL-5 gene transcription in IL-5 producing T cell clones. PBMC of some intrinsic asthmatics produced IL-5 in response to mite allergen extract. T cell clones established from such patients did produce IL-5 in response to mite allergen, suggesting that mite allergen might be in part responsible for so called "intrinsic" asthma.