Attenuation of lymphocyte immune responses during Mycobacterium avium complex-induced lung disease due to increasing expression of programmed death-1 on lymphocytes.
Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing prevalence. Attenuated cellular immunity associated with programmed cell death (PD)-1 may play a pathophysiological role in MAC-LD but lacks of investigation. We enrolled 80 participants in this prospective study, including 50 with MAC-LD and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs), lymphocytes and monocyte-derived macrophages were used for MAC antigen stimulation. Patients with MAC-LD had lower tumor necrosis factor-α and interferon-γ responses compared to the healthy controls in PBMC stimulation assays with MAC bacilli. These responses improved after MAC treatment. The PD-1 and PD ligand expressions and apoptosis were higher in the lymphocytes of the patients with MAC-LD compared to the controls. Both PD-1 and apoptosis on T lymphocytes were significantly increased in the patients with MAC-LD, either by direct MAC stimulation or by MAC-primed macrophage activation. Partially blocking PD-1 and the PD ligand with antagonizing antibodies in the stimulation assay significantly increased the cytokine production of IFN-γ and decreased the apoptosis on T lymphocytes. In conclusion, the patients with MAC-LD have attenuated lymphocyte immunity, which might be associated with increasing activation of PD-1 and PD-1 ligand. Regulating such activation might improve the lymphocytic secretion of IFN-γ and reduce apoptosis.
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan.
Chin-Chung
CC
Shu
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Jann-Yuan
JY
Wang
Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Ming-Fang
MF
Wu
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Chen-Tu
CT
Wu
Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Tao-Yuan, Taiwan.
Hsin-Chih
HC
Lai
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Department of Laboratory Medicine, and National Taiwan University Hospital, Taipei, Taiwan.
Li-Na
LN
Lee
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Bor-Luen
BL
Chiang
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Chong-Jen
CJ
Yu
D017209:Apoptosis; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D015269:Mycobacterium avium Complex / Q000276:immunology*; D015270:Mycobacterium avium-intracellulare Infection / Q000150:complications*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism*; D011446:Prospective Studies
D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor