Department of Biological Chemistry, University of Buenos Aires, School of Sciences, Buenos Aires, Argentina.
Immunol Cell Biol. 2012 Apr;90(4):449-56. doi: 10.1038/icb.2011.63. Epub 2011 Jul 12.
Protective immunity against Mycobacterium tuberculosis is primarily mediated by the interaction of antigen-specific T cells and antigen presenting cells, which often depends on the interplay of cytokines produced by these cells. Costimulatory signals represent a complex network of receptor-ligand interactions that qualitatively and quantitatively influence immune responses. Thus, here we investigated the function of CD137 and CD137L, molecules known to have a central role in immune regulation, during human tuberculosis (TB). We demonstrated that M. tuberculosis antigen stimulation increased both CD137 and CD137L expression on monocytes and NK cells from TB patients and healthy donors, but only up-regulated CD137 on T lymphocytes. Blockage of the CD137 pathway enhanced the levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by monocytes and NK against M. tuberculosis. In contrast, CD137 blockage significantly decreased the specific degranulation of CD8(+) T cells and the percentage of specific IFN-γ and TNF-α producing lymphocytes against the pathogen. Furthermore, inhibition of the CD137 pathway markedly increased T-cell apoptosis. Taken together, our results demonstrate that CD137:CD137L interactions regulate the innate and adaptive immune response of the host against M. tuberculosis.
针对结核分枝杆菌的保护性免疫主要是通过抗原特异性 T 细胞和抗原提呈细胞的相互作用介导的，而这通常依赖于这些细胞产生的细胞因子的相互作用。共刺激信号代表了受体-配体相互作用的复杂网络，这些相互作用在质量和数量上影响着免疫反应。因此，在这里我们研究了 CD137 和 CD137L 在人类结核病 (TB) 中的功能，这两种分子在免疫调节中起着核心作用。我们证明了结核分枝杆菌抗原刺激可增加 TB 患者和健康供体的单核细胞和 NK 细胞上 CD137 和 CD137L 的表达，但仅上调 T 淋巴细胞上的 CD137。阻断 CD137 通路可增强单核细胞和 NK 细胞针对结核分枝杆菌产生的干扰素 (IFN)-γ 和肿瘤坏死因子 (TNF)-α 的水平。相比之下，CD137 阻断显著降低了针对病原体的 CD8(+) T 细胞特异性脱颗粒和特异性 IFN-γ 和 TNF-α 产生淋巴细胞的百分比。此外，抑制 CD137 通路可显著增加 T 细胞凋亡。总之，我们的结果表明 CD137:CD137L 相互作用调节宿主针对结核分枝杆菌的固有和适应性免疫反应。
