Table 1.

Summary of studies investigating conventional T cell immune exhaustion in NTM-LD.

Study ID	Patients included	NTM species	Phenotypic properties	Functional properties
Shu et al. Scientific Reports, 2017	80 participants: - 50 MAC-LD - 30 HC	MAC	Lymphocytes of patients with MAC-LD have higher PD-1, PD-L1 and apoptosis markers expressions than those of healthy controls.	Patients with MAC-LD had lower TNF-α and IFN-γ responses compared to HC in PBMC stimulation assays with MAC bacilli. MAC therapy improved the secretion of TNF-α and IFN-γ. Partially blocking PD-1 and the PD-L1 with antagonizing antibodies significantly increased the cytokine production of IFN-γ of MAC-LD.
Han et al. Journal of Clinical Medicine, 2020	91 participants: - 71 MAC-LD - 20 HC	MAC	In patients with MAC-LD, CD4+ T cells and CD4+IL-17+ T cells frequencies decreased and CD4+IL-4+ T cells and CD4+CD25+Foxp3+ T cells (Tregs) increased after MAC stimulation compared to HC PBMC. MAC-LD patients have an increased PD-1, CTLA-4, and TIM-3-expression on T cells in response to MAC-stimulation compared to HC in PBMC.	Patients with MAC-LD had lower IFN-γ, IL-17A, IL-10 production compared to HC in PBMC stimulation assays with MAC bacilli.
Wang et al. Frontiers in Immunology, 2021	93 participants: - 47 MAC-LD - 46 HC	MAC	Patients with MAC-LD have a higher TIM3+ expression on CD4+ and CD8+ T cells compared to HC.	Patients with MAC-LD had higher cell apoptosis and specific cytokine attenuation (↓ secretion of IL-2, TNF-α, IFN-γ) compared to HC in PBMC stimulation assays MAC therapy (11 patients) decreased the TIM3+ expression on CD4+T and CD8+T cells after 2 months.
Shu C.C. et al. Journal of Clinical Medicine, 2019	96 participants: - 46 MAC-LD - 23 MABS-LD - 27 HC	MAC MABS	In the MAC-LD group, frequencies of PD-1+CD4+ T cell were higher than in HC and in MAB-LD patients. In the MAC-LD cohort were identified MAC subspecies: patients with M. intracellulare and M. avium have higher expression of PD-1 on CD4+ T cell compared to other subspecies (M. chimera and M.timonense) in the same cohort. No intergroup differences regarding CTLA-4+CD4+ and Treg cells frequencies. The proportion of MDSCs was higher in the MAC-LD and MAB-LD groups than among HC.	No functional properties are available: this article analysed association of phenotypic properties with clinical features and radiographic outcomes.
Lutzky VP et al. Frontiers in immunology, 2018	34 participants: - cohort of 24 CF patients: (CFAct) 7 with active pulmonary MABS infection; (CFPast) 8 with previous diagnosis of MABS infection; (CFControl) 9 with no history of or current NTM infection - cohort of 10 elderly patients: who had active or past NTM infection; HC	MABS	- Comparison of Tregs (CD4+ CD25+ FOXP3+): → higher percentages in CFAct and CFPast groups compared to the CFControl → in elderly cohort were higher in NTM patients compared to healthy controls. - CD25+, CTLA-4, and PD-1 on CD4+ T cells revealed a common fingerprint in CFAct and CFPast groups which was distinct from the CFControl group - no difference between CF patients with active or past NTM-PD and HC in terms of T cell fingerprint	- Post-mitogen stimulation TNFα-producing CD4+ T cells were significantly lower in both CFAct and CFPast groups compared to the CFControl group - Increased IFNγ secretion was seen in both CD4+ and CD8+ T cells in the CF NTM cohort compared to healthy controls; in the elderly NTM cohort, there was no significant increase in IFNγ-secreting cells in both CD4+ or CD8+ T cells.

NTM, non-tuberculous mycobacteria; MAC, M. avium complex; MAC-LD, MAC - lung disease; MABS, M. abscessus complex; HC, healthy controls; PBMC, peripheral blood mononuclear cells; MDSCs, Myeloid-derived suppressor cells; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; PD-1, programmed cell death protein 1; TIM-3, T-cell immunoglobulin domain and mucin domain 3; CF, cystic fibrosis.