Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Eur J Immunol. 2013 Jun;43(6):1568-77. doi: 10.1002/eji.201243262.
Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8(+) T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8(+) T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8(+) T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8(+) T cells in LTBI subjects were mostly T EMRA cells (CD45RA(+) CCR7(-)), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA(-) CCR7(-)), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8(+) T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8(+) T cells expressed perforin and granulysin. Finally, Mtb-specific CD8(+) T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8(+) T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8(+) T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.
结核分枝杆菌（Mtb）的保护性免疫仍知之甚少，Mtb 特异性 CD8(+)T 细胞的作用存在争议。在这里，我们对 326 例潜伏性 Mtb 感染（LTBI）或活动性结核病（TB）患者的 Mtb 特异性 CD8(+)T 细胞进行了广泛的表型和功能特征分析。大多数（60%）TB 患者和少数（15%）LTBI 患者中都检测到 Mtb 特异性 CD8(+)T 细胞，但数量相当。LTBI 患者的 Mtb 特异性 CD8(+)T 细胞主要为 T EMRA 细胞（CD45RA(+)CCR7(-)），共表达 2B4 和 CD160，而 TB 患者的 Mtb 特异性 CD8(+)T 细胞主要为 TEM 细胞（CD45RA(-)CCR7(-)），表达 2B4 但缺乏 PD-1 和 CD160。两组细胞的细胞因子谱没有明显差异。此外，Mtb 特异性 CD8(+)T 细胞表达低水平的穿孔素和颗粒酶，但含有颗粒酶 A 和 B。然而，体外扩增的 Mtb 特异性 CD8(+)T 细胞表达穿孔素和颗粒酶。最后，与肺结核患者相比，肺外结核病患者中较少检测到 Mtb 特异性 CD8(+)T 细胞反应。与肺结核患者相比，肺外结核病患者的 Mtb 特异性 CD8(+)T 细胞增殖也更大。因此，Mtb 感染的活性和临床表现与 Mtb 特异性 CD8(+)T 细胞反应的不同特征有关。这些结果为 Mtb 与宿主免疫反应之间的相互作用提供了新的见解。
