树突状细胞对呼吸道合胞病毒感染T细胞免疫反应的调节作用  

Dendritic cells regulate T cell immune responses to respiratory syncytial virus

作　　者：鲍一笑[1] 华丽[1] 吕婕[1] 董晓艳[1] 林芊[1] 齐磊[1] 叶剑敏[1] 

机构地区：[1]上海交通大学医学院附属新华医院儿内科,上海200092

出　　处：《临床儿科杂志》2007年第12期1020-1024,共5页Journal of Clinical Pediatrics

摘　　要：目的研究在呼吸道合胞病毒(RSV)感染过程中树突状细胞(dendritic cell,DC)的数量和功能变化,探讨其对T细胞免疫反应的调节作用。方法BALB/c小鼠感染RSV后,分离并用流式细胞仪检测肺DC的数量和成熟标志;分离肺淋巴细胞并在体外培养,ELISA测定培养上清中Th2和Th1细胞因子的水平;在体外RSV或流感病毒(IFZ)感染骨髓衍生树突状细胞(BMDC)48 h,检测培养体系上清中IL-12、IL-10水平。在BMDC和T淋巴细胞共培养体系中加入重组IL-10,观察对T细胞分泌细胞因子的影响。结果RSV感染小鼠肺淋巴细胞在体外培养情况下IL-13、IL-4和IL-5分泌显著增加,均高于IFZ感染小鼠(P均<0.01);IFN-γ分泌水平在RSV或IFZ感染小鼠均升高,但两者间差异无统计学意义(P>0.05)。RSV感染小鼠后3 d,肺DC数量增多,DC成熟标记分子MHCⅡ-Ia、CD86和CD80表达增加(P均<0.01);IFZ感染BMDC 48 h,培养上清中IL-10显著增高(P<0.01),而在RSV感染组不升高(P>0.05)。在BMDC和T淋巴细胞共培养体系中加入重组IL-10后,IFN-γ的分泌水平显著增加,IL-13和IL-5的分泌水平受到抑制(P均<0.01)。结论RSV感染过程中,DC数量增加,成熟度提高,但分泌IL-10不足,通过补充外源性IL-10实验证明这是RSV感染引起Th2反应为主的原因之一。[临床儿科杂志,2007,25(12):1020-1024]Objectives To detect the changes of quantity and function of dendritic cells （DCs） during RSV （respiratory syncytial virus） infection and explore the mechanism that DCs regulate the T cell immune response to RSV infection. Methods Lung DC numbers and the expression of the matured marker on lung DCs were studied with flow cytometry in RSV infected BALB/c mice. Lung lymphocytes were isolated and cultured in vitro. Levels of Th2 and Th1 in cultured supernatant were measured with ELISA analysis. Bone marrow （BM） derived DCs （BMDCs） cultured for 48 hours in vitro following RSV or IFZ infection, and levels of IL-12 and IL-10 in cultured supernatant were also measured. Recombinant IL-10 was added into BMDC co-cultured with T lymphocytes. Effect of IL-10 on cytokine release of T lymphocytes was investigated. Results RSV infection was associated with increased production of IL-13, IL-4, and IL-5 as compared to IFZ infection in vitro. Cultured lung lymphocytes secreted similar levels of IFN-γ production following RSV or IFZ infection. Increased lung DC numbers, the expression of MHC class Ⅱ, CD86, and CD80 on lung DCs were observed on day 3 in RSV infected mice. In cultured BMDCs, both RSV and IFZ induced IL-12 production to a similar extent. Interestingly, IFZ, but not RSV, increased IL-10 production from the BMDCs. IFN-γ production significantly increased, while the secretion of IL-13 and IL-5 were suppressed when recombinant IL-10was added into BMDCs co-cultured with T lymphocytes. Conclusions These studies indicate that RSV favors Th2 immune response in part by interacting with DCs. This results in an enhancement of Th2 cell differentiation and inhibition of IL-10 secretion, suggesting a central role for DC-mediated regulation of T cell commitment in the adaptive immune response to RSV.

关 键 词：呼吸道合胞病毒 树突状细胞 T细胞 IL-IO 

分 类 号：R392[医药卫生—免疫学]