Hu Wei-Kun, Lu Xiao-Xia, Yang Shuo, Xu Guo-Peng, Lan Fen, Chen Shi-Xin, Ni Wang, Xiong Wei-Ning, Xiong Sheng-Dao
Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
J Asthma. 2009 Nov;46(9):872-7. doi: 10.3109/02770900903199953.
T-cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) is preferentially expressed on Th1-helper type T-cells and functions to repress the Th1-mediated immune response. However, the role of Tim-3 during the inflammatory pathogenesis of asthma remains unclear. This study determines the expression level of Tim-3 in CD4+ T-cells within the peripheral blood and bronchoalveolar lavage fluid (BALF) isolated from a murine model of atopic asthma and explores the potential role of Tim-3 during the inflammatory response. Mice were randomly divided into normal control, asthma day 1, and asthma day 7 groups, and peripheral blood T lymphocytes and BALF cells were collected. The ratio of Tim-3+/CD4+ cells among the total CD4+cell populations from peripheral blood and BALF was determined by flow cytometry, and the expression of the Tim-3 mRNA was determined by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). In contrast with the normal control group, the ratio of Tim-3+/CD4+:CD4+ cells and the level of Tim-3 mRNA in both the peripheral blood T lymphocytes and BALF cells among the asthma day 1 and asthma day 7 groups were significantly increased (p < 0.01), and those in the asthma day 7 group were higher than the asthma day 1 group (p < 0.05). There was also a positive correlation between the ratio of Tim-3+/CD4+:CD4+ detected in BALF and that the ratio detected in peripheral blood T lymphocytes (r = 0.84, p < 0.01). Therefore, the expression of Tim-3 is increased in CD4+ T-cells following airway challenge and likely affects asthma-induced inflammation by repressing the Th1-mediated immune response.
含T细胞免疫球蛋白和粘蛋白结构域分子3(Tim-3)优先表达于辅助性1型T细胞(Th1),其功能是抑制Th1介导的免疫反应。然而,Tim-3在哮喘炎症发病机制中的作用仍不清楚。本研究测定了从变应性哮喘小鼠模型分离的外周血和支气管肺泡灌洗液(BALF)中CD4⁺T细胞内Tim-3的表达水平,并探讨了Tim-3在炎症反应中的潜在作用。将小鼠随机分为正常对照组、哮喘第1天组和哮喘第7天组,收集外周血T淋巴细胞和BALF细胞。通过流式细胞术测定外周血和BALF中总CD4⁺细胞群体中Tim-3⁺/CD4⁺细胞的比例,通过逆转录聚合酶链反应(RT-PCR)测定Tim-3 mRNA的表达。与正常对照组相比,哮喘第1天组和哮喘第7天组外周血T淋巴细胞和BALF细胞中Tim-3⁺/CD4⁺:CD4⁺细胞的比例以及Tim-3 mRNA水平均显著升高(p<0.01),且哮喘第7天组高于哮喘第1天组(p<0.05)。BALF中检测到的Tim-3⁺/CD4⁺:CD4⁺比例与外周血T淋巴细胞中检测到的比例之间也呈正相关(r=0.84,p<0.01)。因此,气道激发后CD4⁺T细胞中Tim-3的表达增加,可能通过抑制Th1介导的免疫反应影响哮喘诱导的炎症。