摘要
目的:研究抗ICOS抗体对哮喘大鼠外周血和淋巴液来源CD4+CD25+Foxp3+调节性T细胞(Treg)数量及其功能的影响。方法:抗ICOS抗体处理血液和淋巴液中单个核细胞(MNC),流式细胞仪检测MNC中CD4+CD25+Foxp3+T细胞百分率,酶联免疫吸附试验(ELISA)检测MNC培养液上清IL-10和TGF-β1含量。结果:末次激发后各个时间点收集MNC,体外培养96 h,各组淋巴液来源MNC体外培养体系中CD4+CD25+Foxp3+Treg细胞百分率均显著高于血液(P<0.05),哮喘组淋巴液和血液来源MNC体外培养体系中CD4+CD25+Foxp3+Treg细胞百分率均显著低于正常对照组(P<0.05),抗ICOS抗体组淋巴液和血液来源MNC体外培养体系中CD4+CD25+Foxp3+Treg细胞百分率显著低于哮喘组(P<0.05)。末次激发后0 h收集淋巴液来源和血液来源MNC培养上清中抗ICOS抗体组IL-10显著低于哮喘组和正常对照组(P<0.05);末次激发后不同时间点收集MNC培养上清中各组TGF-β1无明显差别。结论:用抗ICOS抗体阻断ICOS/ICOSL信号通路加重哮喘大鼠Treg细胞缺陷,并在哮喘激发早期0 h抑制血液和淋巴液来源MNC体外培养体系中CD4+CD25+Foxp3+Treg细胞分泌IL-10,但对于TGF-β1分泌无显著影响。
AIM： To investigate the influences of anti- ICOS antibody （anti-ICOSAb） on quantity and function of CD4 ＋ CD25 ＋ Foxp3＋ Treg cells from lymph and peripheral blood of rats with bronchial asthma. METHODS： The mononuclear cells （MNC） from lymph and blood were co-cultured with anti-ICOSAb, and then the percentage of CD4 ＋ CD25 ＋ Foxp3 ＋Treg cells were analyzed by flow cytometer （FCM） and the levels of IL-10 and TGF-β1 in supernatants were determined by ELISA. RESULTS： The MNC were collected from lymph and blood at 0, 24 and 48 h after the last challenge, respectively, and the cells were cul- tured for 96 h in vitro. The percentage of CD4＋ CD25＋ Foxp3 ＋ Treg cells in the MNC from lymph was significantly higher than that from blood in each group （ P 〈 0.05） ; The percentage of CD4 ＋CD25 ＋ Foxp3＋Treg cells in the MNC from lymph and blood in asthma group was significantly low- er compare with the normal control group （ P 〈 0. 05 ） ; The percentage of CD4＋ CD25 ＋ Foxp3 ＋ Treg cells in the MNC from lymph and blood in the anti-ICOSAb group obviously decreased compare with the asthma group （ P 〈 0.0.5 ）. At 0 h after the last challenge, the level of IL-10 in the superna- tant of MNC from lymph and blood in the anti-ICOSAb group were significantly lower than that of the control and asthma groups （P 〈 0.05）, while there were no significant differ- ences of TGF-β1 expression in the supernatant of MNC from lymph and blood in each group at different time points. CON-CLUSION： Blocking the ICOS/ICOSL signaling pathway by anti-ICOSAb could exacerbate the deficiency of CD4＋ CD25＋ Foxp3 ＋ Treg cells from lymph and blood in bronchial asthmatic rat, meanwhile inhibit the CD4＋ CD25 ＋ Foxp3 ＋ Treg cells secre- ting IL-10 at 0 h after the last challenge, but have no significant effect on the secretion of TGF-β1.
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2012年第10期1029-1032,1036,共5页
Chinese Journal of Cellular and Molecular Immunology
基金
山东省自然科学基金(ZR2010HM0854)
山东省自然科学基金(ZR2011HM081)
