Lung and blood mononuclear cell responses of tuberculosis patients to mycobacterial proteins
Lung and blood mononuclear cell responses of tuberculosis patients to mycobacterial proteins
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DOI：
10.1183/09031936.00111205
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发表时间：
2007-02-01
影响因子：
24.3
通讯作者：
Khuller, G. K.
中科院分区：
文献类型：
--
作者：
Sable, S. B.;Goyal, D.;Khuller, G. K.
本研究采用支气管肺泡灌洗液（BAL）和外周血单个核细胞（PBMCs）检测了结核分枝杆菌抗原（Ag）对人肺和外周血淋巴细胞的特异性差异，并与非结核分枝杆菌抗原（Ag）进行了比较。Ag85B、CFP-31、CFP-22.5、CFP-21、M.发现结核蛋白-64和一种尚未表征的19 kDa蛋白主要被TB患者的BAL细胞识别，这是基于淋巴细胞增殖和显著的干扰素-γ释放。而CFP-8、6-kDa早期分泌抗原靶点、CFP-10、CFP-14.5、M.发现结核分泌蛋白-17和五种其它尚未表征的低分子量多肽在PBMC水平的淋巴细胞增殖基础上是高的。此外，BAL巨噬细胞，而不是血液单核细胞，被发现产生一氧化氮（NO）的分枝杆菌抗原。在主要被BAL淋巴细胞识别的多肽中，只有Ag 85 A和Ag 85 B被发现同时诱导肺泡巨噬细胞产生NO和白细胞介素-12（p40）。并且还提示了抗原85复合物多肽用于开发未来的粘膜抗结核疫苗的用途。
The differences in specificity of human lung and peripheral lymphocytes for mycobacterial antigens (Ag) need to be evaluated in order to identify vaccine candidates against pulmonary tuberculosis (TB).Therefore, the present study examined the response to low molecular weight secretory proteins of Mycobacterium tuberculosis in bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMCs) from minimal pulmonary TB and non-TB patients.Ag85A, Ag85B, culture filtrate protein (CFP)-31, CFP-22.5, CFP-21, M. tuberculosis protein-64 and an as yet uncharacterised 19 kDa protein were found to be predominantly recognised by BAL cells of TB patients on the basis of lymphocyte proliferation and significant interferon-gamma release. However, recognition of CFP-8, 6-kDa early secreted antigenic target, CFP-10, CFP-14.5, M. tuberculosis secretory protein-17 and five other as yet uncharacterised low molecular weight polypeptides was found to be high on the basis of lymphocyte proliferation at the level of PBMCs. Furthermore, BAL macrophages, and not blood monocytes, were found to produce nitric oxide (NO) in response to mycobacterial Ags. Among polypeptides predominantly recognised by BAL lymphocytes, only Ag85A and Ag85B were found to induce both NO and interleukin-12 (p40) by alveolar macrophages.In conclusion, the present results indicate heterogeneity in antigen recognition by bronchoalveolar lavage cells and peripheral mononuclear blood cells of minimal tuberculosis patients, and also suggest the utility of antigen 85 complex polypeptides for the development of a future mucosal antituberculous vaccine.