Xu Ya-Qing, Gao Ya-Dong, Yang Jiong, Guo Wei
Department of Respiratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan, China.
J Asthma. 2010 May;47(4):367-73. doi: 10.3109/02770903.2010.481340.
The suppressive cytokine interleukin-10 (IL-10) plays a central role in disease control and clinical therapies of asthma. CD46 was recently identified as costimulatory molecule in inducing IL-10-producing regulatory T cells type 1 (Tr1) from CD4(+) T cells. Alterations in CD46 costimulation pathway were shown to be associated with multiple sclerosis and hemodialysis. In this study, the authors investigated alterations in CD46 costimulatory pathway in asthma.
CD4(+)CD25(+) regulatory T cells (Tregs) and CD4(+)CD25(-) T cells were isolated from peripheral blood mononuclear cells (PBMCs) of asthma patients (n = 13) and healthy subjects (n = 17). Both subsets of CD4(+) T cells were cultured alone or cocultured at a ratio of 1:10 under stimulation with CD3/CD28 or CD3/CD46, and the production of IL-10 in the supernatants was assessed by enzyme-linked immunosorbent assay (ELISA), the proliferation rates of the cells were determined with thymidine incorporation assay.
Levels of IL-10 in the supernatants were higher in undivided CD4(+) T cells and 1:10 cocultured CD4(+)CD25(+) Tregs/CD4(+)CD25(-) T cells than in CD4(+)CD25(+) Tregs or CD4(+)CD25(-) T cells alone, either under CD46 or under CD28 costimulation, both in healthy controls (n = 9) and in asthma patients (n = 7). Under anti-CD3/CD46 stimulation, IL-10 production in undivided CD4(+) T cells and cocultured T cells from asthma patients was lower than that in healthy controls. When treated with glucocorticoids, IL-10 production in undivided CD4(+) T cells and 1:10 cocultured CD4(+) T cells was not different between asthma patients (n = 6) and healthy controls (n = 8). The proliferation rates and the surface expression of CD46 were not different in T cells from both groups.
This study identified a new functional defect of CD4(+)CD25(+) Tregs in inducing IL-10 production from CD4(+)CD25(-) T cells under CD46 costimulation in asthma patients, which may be involved in the pathogenesis of allergic asthma.
抑制性细胞因子白细胞介素-10（IL-10）在哮喘的疾病控制和临床治疗中起核心作用。CD46最近被确定为从CD4(+) T细胞诱导产生IL-10的1型调节性T细胞（Tr1）的共刺激分子。已表明CD46共刺激途径的改变与多发性硬化症和血液透析有关。在本研究中，作者调查了哮喘中CD46共刺激途径的改变。
从哮喘患者（n = 13）和健康受试者（n = 17）的外周血单个核细胞（PBMC）中分离出CD4(+)CD25(+)调节性T细胞（Tregs）和CD4(+)CD25(-) T细胞。将这两个CD4(+) T细胞亚群单独培养或以1:10的比例在CD3/CD28或CD3/CD46刺激下共培养，通过酶联免疫吸附测定（ELISA）评估上清液中IL-10的产生，用胸苷掺入法测定细胞的增殖率。
在健康对照者（n = 9）和哮喘患者（n = 7）中，无论是在CD46还是在CD28共刺激下，未分离的CD4(+) T细胞以及1:10共培养的CD4(+)CD25(+) Tregs/CD4(+)CD25(-) T细胞上清液中的IL-10水平均高于单独的CD4(+)CD25(+) Tregs或CD4(+)CD25(-) T细胞。在抗CD3/CD46刺激下，哮喘患者未分离的CD4(+) T细胞和共培养T细胞中IL-10的产生低于健康对照者。用糖皮质激素处理后，哮喘患者（n = 6）和健康对照者（n = 8）未分离的CD4(+) T细胞以及1:10共培养的CD4(+) T细胞中IL-10 的产生没有差异。两组T细胞的增殖率和CD46的表面表达没有差异。
本研究发现哮喘患者中CD4(+)CD25(+) Tregs在CD46共刺激下诱导CD4(+)CD25(-) T细胞产生IL-10存在新的功能缺陷，这可能参与过敏性哮喘的发病机制。
