Mori A, Suko M, Kaminuma O, Nishizaki Y, Mikami T, Ohmura T, Hoshino A, Inoue S, Tsuruoka N, Okumura Y, Sato G, Ito K, Okudaira H
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Int Immunol. 1996 Dec;8(12):1889-95. doi: 10.1093/intimm/8.12.1889.
The role of IL-2 in IL-5 synthesis of human helper T cells was investigated. All of the Der f II (a major allergen of house dust mite)-specific T cell clones established from atopic asthmatic patients produced both IL-2 and IL-4 upon activation (Th0 phenotypes). Recombinant IL-2 induced gene expression and protein synthesis of IL-5 in T cell clones that produced IL-5 upon antigenic stimulation. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell clones was clearly transcribed in response to IL-2, indicating that the approximately 500 bp gene segment 5' upstream of the coding region was functionally sufficient for the gene transcription induced by IL-2. IL-2-induced IL-5 synthesis as well as proliferation was dependent on tyrosine kinases. Moreover, IL-5 production by T cell clones stimulated with immobilized anti-CD3 antibody was completely abrogated by anti-IL-2 neutralizing antibody, suggesting that IL-5 (a Th2 cytokine) synthesis of human helper T cells is dependent on IL-2 (a Th1 cytokine). Our present findings clearly demonstrated that IL-2, known as a T cell growth factor, exerts a cytokine promoting activity on T cells. IL-2 produced at the site of allergic inflammation might facilitate eosinophilic inflammation by inducing IL-5 production in T cells.
研究了白细胞介素-2（IL-2）在人辅助性T细胞白细胞介素-5（IL-5）合成中的作用。从特应性哮喘患者中建立的所有粉尘螨主要变应原Der f II特异性T细胞克隆在激活后均产生IL-2和IL-4（Th0表型）。重组IL-2在抗原刺激下能诱导产生IL-5的T细胞克隆中IL-5的基因表达和蛋白质合成。转染至T细胞克隆的人IL-5启动子/增强子-荧光素酶基因构建体在IL-2作用下明显转录，表明编码区上游约500 bp的基因片段在功能上足以介导IL-2诱导的基因转录。IL-2诱导的IL-5合成以及增殖依赖于酪氨酸激酶。此外，固定化抗CD3抗体刺激的T细胞克隆产生的IL-5被抗IL-2中和抗体完全消除，这表明人辅助性T细胞的IL-5（一种Th2细胞因子）合成依赖于IL-2（一种Th1细胞因子）。我们目前的研究结果清楚地表明，作为T细胞生长因子的IL-2对T细胞具有细胞因子促进活性。在变应性炎症部位产生的IL-2可能通过诱导T细胞产生IL-5来促进嗜酸性粒细胞炎症。
