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

• Main Authors: Chin-Chung Shu, Sheng-Wei Pan, Jia-Yih Feng, Jann-Yuan Wang, Yu-Jiun Chan, Chong-Jen Yu, Wei-Juin Su
• Format: Article
• Language: English
• Published: MDPI AG 2019-05-01
• Series: Journal of Clinical Medicine
• Subjects: cytotoxic T-lymphocyte antigen-4; <i>Mycobacterium avium</i> complex; <i>Mycobacterium abscessus</i>; myeloid derived suppressor cells; nontuberculous mycobacteria; programmed death-1; regulatory T cells
• Online Access: https://www.mdpi.com/2077-0383/8/5/736
• ISSN: 2077-0383

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 <i>Mycobacterium avium</i> complex (MAC)-LD, 23 with <i>M. abscessus</i> (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 <i>M. intracellulare-</i> and <i>M. avium</i>-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.