Goter-Robinson Carol, Derrick Steven C, Yang Amy Li, Jeon Bo Young, Morris Sheldon L
Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Building 29/Room 509, CBER/FDA, 29 Lincoln Dr., Bethesda, MD 20892, USA.
Vaccine. 2006 Apr 24;24(17):3522-9. doi: 10.1016/j.vaccine.2006.02.005. Epub 2006 Feb 20.
Although vaccination against tuberculosis (TB) was initiated more than 80 years ago, the correlates of protective immunity against infection by Mycobacterium tuberculosis have still not been well defined. To investigate the vaccine-induced immune responses against TB, we evaluated the early pulmonary cytokine responses elicited by a low dose M. tuberculosis aerogenic challenge in mice that had been immunized with either BCG or a TB DNA vaccine cocktail, two vaccine preparations that induce long-term protection in the mouse model of pulmonary TB. Using three different assays, we showed that specific cytokine responses were elevated in the lungs of vaccinated mice (relative to naïve controls) during the second week post-challenge. By measuring cytokine levels in the bronchoalveolar lavage fluid (BAL) and cytokine mRNA concentrations in pulmonary cells, the levels of IFN-gamma, IL-12, and RANTES were shown to be elevated from days 7-14 post-challenge in the lungs. By intracellular cytokine staining (ICS), increased numbers of lung CD4 and CD8 cells expressing IFN-gamma were also seen at days 10 and 14 after the infection. Moreover, increased post-challenge IFN-gamma levels were detected using the ICS and cytokine mRNA assays in aging BCG-immunized mice that had been effectively boosted with a TB DNA vaccine. Taken together, these data suggest that the post-infection induction of early type 1 cytokine responses correlate with the induction of long-term protective immunity in vaccinated mice.
尽管针对结核病（TB）的疫苗接种始于80多年前，但针对结核分枝杆菌感染的保护性免疫的相关因素仍未得到明确界定。为了研究疫苗诱导的针对结核病的免疫反应，我们评估了用卡介苗（BCG）或结核DNA疫苗混合物免疫的小鼠在受到低剂量结核分枝杆菌气溶胶攻击后早期肺部细胞因子的反应，这两种疫苗制剂在肺结核小鼠模型中可诱导长期保护。通过三种不同的检测方法，我们发现，在攻击后的第二周，接种疫苗的小鼠肺部（相对于未免疫的对照）的特异性细胞因子反应有所升高。通过测量支气管肺泡灌洗液（BAL）中的细胞因子水平和肺部细胞中的细胞因子mRNA浓度，发现攻击后第7 - 14天肺部的干扰素-γ（IFN-γ）、白细胞介素-12（IL-12）和调节激活正常T细胞表达和分泌的趋化因子（RANTES）水平升高。通过细胞内细胞因子染色（ICS），在感染后第10天和第14天也观察到肺部表达IFN-γ的CD4和CD8细胞数量增加。此外，在已用结核DNA疫苗有效加强免疫的老龄卡介苗免疫小鼠中，使用ICS和细胞因子mRNA检测方法检测到攻击后IFN-γ水平升高。综上所述，这些数据表明，感染后早期1型细胞因子反应的诱导与接种疫苗小鼠长期保护性免疫的诱导相关。
