Determinants and kinetics of cytokine expression patterns in lungs of vaccinated mice challenged with respiratory syncytial virus.
Determinants and kinetics of cytokine expression patterns in lungs of vaccinated mice challenged with respiratory syncytial virus.
复制标题
呼吸道合胞病毒攻击的接种小鼠肺部细胞因子表达模式的决定因素和动力学。
DOI：
10.1016/s0264-410x(96)00214-9
复制
发表时间：
1997
期刊：
影响因子：
5.5
通讯作者：
Graham,BS
中科院分区：
文献类型：
--
作者：
Tang,YW;Neuzil,KM;Fischer,JE;Robinson,FW;Parker,RA;Graham,BS
通过更好地理解自然疾病和疫苗增强型疾病的发病机制，将推动成功的呼吸道合胞病毒(RSV)疫苗的开发。利用小鼠模型，我们检测了用灭活或活的抗原启动并用RSV攻击的小鼠肺内细胞因子的信息表达和细胞因子的分泌。如果初始攻击间隔为2周，则可获得稳定的细胞因子mRNA表达。白介素4(IL-4)和干扰素-γ(干扰素-γ)的表达模式在攻击后第4天建立，并至少维持到第12天，不受免疫原浓度和病毒攻击的影响。酶联免疫斑点分析表明，CD_4~+T细胞负责产生IL-4，而许多细胞类型分泌干扰素-γ。这些实验开始确定RSV感染后细胞因子表达的动力学和细胞因子产生细胞的表型，支持先前的发现，即CD4+T淋巴细胞的异常渗透和IL-4的过度分泌可能在疫苗增强的RSV相关疾病中发挥作用。
The development of a successful respiratory syncytial virus (RSV) vaccine will be advanced by an improved understanding of the pathogenesis of natural disease and vaccine-enhanced illness. Using a murine model, we have examined cytokine message expression and cytokine secretion in lungs of mice primed with killed or live antigens and challenged with RSV. Stable cytokine mRNA expression was achieved if the prime-challenge interval was 2 weeks. The pattern of expression of interleukin-4 (IL-4) and interferon-γ (IFN-γ) mRNA was established by day 4 after challenge and was maintained at least through day 12, and was not affected by the concentration of priming immunogen or virus challenge. An enzyme-linked immunospot assay demonstrated that CD4+ T cells were responsible for the production of IL-4, while many cell types secreted IFN-γ. These experiments begin to define the kinetics of cytokine expression and phenotypes of cytokine-producing cells following RSV infection, supporting previous findings that suggested aberrant infiltration of CD4+ T lymphocytes and excessive IL-4 secretion may play a role in the vaccine-enhanced disease associated with RSV.