The Clinical Significance of Programmed Death-1, Regulatory T Cells and Myeloid Derived Suppressor Cells in Patients with Nontuberculous Mycobacteria-Lung Disease

Background: Increasing expression of programmed death-1 (PD-1) in patients with nontuberculous mycobacteria lung disease (NTM-LD) has been reported, but its role in clinical characteristics and outcomes remains unclear. Methods: We enrolled 96 participants, including 46 with Mycobacterium avium complex (MAC)-LD, 23 with M. abscessus (MAB)-LD, and 27 controls. We measured expressions of PD-1, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and regulatory T (Treg) cells on CD4(+) lymphocytes and myeloid-derived suppressor cells (MDSCs) and analyzed their association with clinical features and radiographic outcomes. Results: The percentage of PD-1 on CD4(+)(PD-1(+)CD4(+)) lymphocytes and MDSCs were higher in the MAC-LD group than the controls. There were no intergroup differences regarding CTLA-4(+)CD4(+) lymphocytes. Higher PD-1(+)CD4(+) lymphocytes were found in M. intracellulare- and M. avium-LD than in other MAC-LD. Positive sputum acid-fast stains and fibrocavitary radiographic lesions were correlated with elevated PD-1(+)CD4(+) lymphocytes and Treg cells. The percentage of PD-1(+)CD4(+) lymphocytes at the initial and 2 months of follow-up significantly predicted subsequent radiographic progression. Conclusion: As markers of immune tolerance, PD-1(+)CD4(+) lymphocytes and MDSCs were higher in MAC-LD patients. The levels of PD-1(+)CD4(+) and Treg cells were correlated with high mycobacteria bacilli burden in NTM-LD. Monitoring the expressions of PD-1(+)CD4(+) lymphocytes may predict radiographic progression.