肺结核中抗原呈递细胞的损伤。
Impairments of Antigen-Presenting Cells in Pulmonary Tuberculosis.
机构信息
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Yadrintsevskaya Street 14, Novosibirsk 630099, Russia.
Novosibirsk Tuberculosis Clinical Hospital No. 1, Vavilova Street 14, Novosibirsk 630082, Russia.
出版信息
J Immunol Res. 2015;2015:793292. doi: 10.1155/2015/793292. Epub 2015 Aug 3.
The phenotype and functional properties of antigen-presenting cells (APC), that is, circulating monocytes and generated in vitro macrophages and dendritic cells, were investigated in the patients with pulmonary tuberculosis (TB) differing in lymphocyte reactivity to M. tuberculosis antigens (PPD-reactive versus PPD-anergic patients). We revealed the distinct impairments in patient APC functions. For example, the monocyte dysfunctions were displayed by low CD86 and HLA-DR expression, 2-fold increase in CD14(+)CD16(+) expression, the high numbers of IL-10-producing cells, and enhanced IL-10 and IL-6 production upon LPS-stimulation. The macrophages which were in vitro generated from peripheral blood monocytes under GM-CSF were characterized by Th1/Th2-balance shifting (downproduction of IFN-γ coupled with upproduction of IL-10) and by reducing of allostimulatory activity in mixed lymphocyte culture. The dendritic cells (generated in vitro from peripheral blood monocytes upon GM-CSF + IFN-α) were characterized by impaired maturation/activation, a lower level of IFN-γ production in conjunction with an enhanced capacity to produce IL-10 and IL-6, and a profound reduction of allostimulatory activity. The APC dysfunctions were found to be most prominent in PPD-anergic patients. The possible role of APC impairments in reducing the antigen-specific T-cell response to M. tuberculosis was discussed.
我们研究了淋巴细胞对结核分枝杆菌抗原反应性不同的肺结核(TB)患者(PPD 反应性与 PPD 无反应性患者)的抗原呈递细胞(APC)表型和功能特性,即循环单核细胞以及体外生成的巨噬细胞和树突状细胞。我们发现患者 APC 功能存在明显缺陷。例如,单核细胞功能障碍表现为 CD86 和 HLA-DR 表达降低、CD14(+)CD16(+)表达增加 2 倍、产生大量 IL-10 的细胞以及 LPS 刺激时 IL-10 和 IL-6 产量增加。GM-CSF 体外从外周血单核细胞生成的巨噬细胞表现为 Th1/Th2 平衡转移(IFN-γ 产量降低与 IL-10 产量增加相结合),以及混合淋巴细胞培养中同种刺激活性降低。GM-CSF + IFN-α体外从外周血单核细胞生成的树突状细胞表现为成熟/激活受损、IFN-γ 产量降低,同时产生 IL-10 和 IL-6 的能力增强,以及同种刺激活性严重降低。在 PPD 无反应性患者中发现 APC 功能障碍最为突出。讨论了 APC 损伤在降低结核分枝杆菌特异性 T 细胞反应中的可能作用。