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PD-1/PD-L pathway inhibits M.tb-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis
The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5141449/ https://www.ncbi.nlm.nih.gov/pubmed/27924827 http://dx.doi.org/10.1038/srep38362 |
Sumario: | The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes. Intracellular cytokine staining was used to determine the PPD-specific IFN-γ-secreting T-cell proportion. CD4(+) T-cell proliferation and macrophage functions were investigated in the presence or absence of PD-1/PD-L pathway blockade. Proportions of both PD-1(+)CD4(+) and PD-L1(+)CD4(+) T cells in ATB patients were more significantly increased than in the HC group (P = 0.0112 and P = 0.0141, respectively). The expressions of PD-1, PD-L1, and PD-L2 on CD14(+) monocytes in ATB patients were much higher than those in the HC group (P = 0.0016, P = 0.0001, and P = 0.0088, respectively). Blockade of PD-1 could significantly enhance CD4(+) T-cell proliferation (P = 0.0433). Phagocytosis and intracellular killing activity of macrophages increased significantly with PD-1/PD-L pathway blockade. In conclusion, the PD-1/PD-L pathway inhibits not only M.tb-specific CD4(+) T-cell-mediated immunity but also innate immunity. |
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