Attenuated lymphocyte immune response inmycobacterium aviumcomplex-lung disease through over-expressed programmed death-1 receptor

Abstract

Background:Mycobacterium avium complex-lung disease (MAC-LD) is important, especially in those with underlying dysfunctional cellular immunity. Programmed cell death (PD)-1 associated attenuated cellular immunity might play a critical pathophysiological mechanism for MAC-LD but lacks of investigation. Methods: This prospective study enrolled 113 participants, including 50 patients with MAC-LD, 33 with MAC pulmonary contamination, and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages were used for MAC antigen stimulation. PD-1, PD ligand, and inflammatory markers on T lymphocytes were measured and compared between the MAC-LD and other groups. Results: Patients with MAC-LD had lower tumor necrosis factor-α and interferon-γ than healthy controls in PBMC stimulation assay by the MAC bacilli. The responses improved after MAC treatment. Using flow cytometry, the expression of PD-1 and PD ligand and apoptosis status were higher in lymphocytes of MAC-LD patients than in those of controls. PD-1 and apoptosis over T lymphocytes were significantly increased in MAC-LD patients, either by MAC directly stimulating or MAC-priming macrophage activation. Blockage of PD1 and PD ligand antibodies in PBMC stimulation assay significantly increased cytokine production and decreased apoptosis over T lymphocytes. Conclusions: Patients with MAC-LD have attenuated lymphocyte immunity and increased apoptosis, probably through PD-1 and PD-1 ligand activation. Blocking these improved both lymphocyte function of secreting IFN-γ and apoptosis. Future targeted therapy involving the PD-1 pathway might be a potential MAC-LD treatment.