Molecular Microbiology Group, COMB, Tropical Biosphere Research Center, Univeristy of the Ryukyus, Okinawa, Japan.
Immunology. 2009 Dec;128(4):556-63. doi: 10.1111/j.1365-2567.2009.03141.x.
Both CD4(+) and CD8(+) T cells are important in protection against Mycobacterium tuberculosis infection. To evaluate the effect of vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) on the CD8(+) T-cell response to pulmonary M. tuberculosis infection, we analyzed the kinetics of CD8(+) T cells specific to the mycobacterial Mtb32a(309-318) epitope, which is shared by M. tuberculosis and M. bovis BCG, in the lung of mice infected with M. tuberculosis. The CD8(+) T cells were detected by staining lymphocytes with pentameric major histocompatibility complex (MHC) class I H-2D(b-)Mtb32a(209-318) peptide complex and were analysed by flow cytometry. Mtb32a-specific CD8(+) T cells became detectable on day 14, and reached a plateau on day 21, in the lung of M. tuberculosis-infected unvaccinated mice. Subcutaneous vaccination with M. bovis BCG in the footpads induced Mtb32a-specific CD8(+) T cells in the draining lymph nodes (LNs) on day 7 and their numbers further increased on day 14. When M. bovis BCG-vaccinated mice were exposed to pulmonaryinfection with M. tuberculosis 4 weeks after vaccination, the Mtb32a-specific CD8(+) T cells in the infected lung became detectable on day 7 and reached a plateau on day 14, which was 1 week earlier than in the unvaccinated mice. The pulmonary CD8(+) T cells from the BCG-vaccinated M. tuberculosis-infected mice produced interferon-gamma in response to Mtb32a(209-318) peptide on day 7 of the infection, whereas those of unvaccinated mice did not. The results demonstrate that induction of mycobacterial antigen-specific protective CD8(+) T cells in the M. tuberculosis-infected lung is accelerated by subcutaneous vaccination with M. bovis BCG.
CD4(+)和 CD8(+)T 细胞在抵抗结核分枝杆菌感染中都很重要。为了评估牛型结核分枝杆菌卡介苗(BCG)接种对结核分枝杆菌肺部感染后 CD8(+)T 细胞反应的影响,我们分析了结核分枝杆菌和牛型结核分枝杆菌 BCG 共有的 Mtb32a(309-318)表位的 CD8(+)T 细胞的动力学,该表位在感染结核分枝杆菌的小鼠肺部用五聚体主要组织相容性复合物(MHC)I 类 H-2D(b-)Mtb32a(209-318)肽复合物染色的淋巴细胞上进行检测,并通过流式细胞术进行分析。在未接种疫苗的感染结核分枝杆菌的小鼠肺部,Mtb32a 特异性 CD8(+)T 细胞在第 14 天即可检测到,并在第 21 天达到平台期。在足底皮下接种 BCG 可诱导接种疫苗的小鼠引流淋巴结(LNs)中 Mtb32a 特异性 CD8(+)T 细胞在第 7 天出现,并在第 14 天进一步增加。当接种疫苗的小鼠在接种疫苗后 4 周暴露于肺部结核分枝杆菌感染时,感染肺部的 Mtb32a 特异性 CD8(+)T 细胞在第 7 天即可检测到,并在第 14 天达到平台期,比未接种疫苗的小鼠早 1 周。来自 BCG 接种的结核分枝杆菌感染小鼠的肺部 CD8(+)T 细胞在感染第 7 天对 Mtb32a(209-318)肽产生干扰素-γ,而未接种疫苗的小鼠则没有。结果表明,皮下接种牛型结核分枝杆菌 BCG 可加速结核分枝杆菌感染肺部中保护性结核分枝杆菌抗原特异性 CD8(+)T 细胞的诱导。
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