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Open AccessArticle

Characteristics of Circulating CD4+ T Cell Subsets in Patients with Mycobacterium avium Complex Pulmonary Disease

by Sun Ae Han 1,†, Yousang Ko 2,†, Sung Jae Shin 3,* and Byung Woo Jhun 1,*
1
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
2
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 05355, Korea
3
Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2020, 9(5), 1331; https://doi.org/10.3390/jcm9051331
Received: 22 February 2020 / Revised: 22 April 2020 / Accepted: 30 April 2020 / Published: 3 May 2020
(This article belongs to the Special Issue Tuberculosis, Drug and Diagnostics Development)
Although prevalence of Mycobacterium avium complex pulmonary disease (MAC-PD) is increasing, limited data are available regarding vulnerability to Mycobacterium avium complex (MAC) infections. To understand the pathobiology of interaction between MAC and host-immunity, it is important to understand the characteristics for circulating T cells in terms of the immunological phenotype and functional correlates in MAC-PD. We aimed to characterize immunophenotype, cytokine profile, and immune inhibitory receptors of circulating CD4+ T cells in MAC-PD patients. We enrolled 71 MAC-PD and 20 control individuals. Flow cytometric analysis was performed to determine T cell subsets and immune checkpoint markers. Ex vivo cytokine productions in response to MAC were determined using enzyme-linked immunosorbent assay. The frequencies of CD4+ T cells and CD4+IL-17+ T cells decreased, while CD4+IL-4+ T cells and CD4+CD25+Foxp3+ T cells increased in peripheral blood mononuclear cells (PBMCs) of MAC-PD individuals upon MAC stimulation compared with those cells in healthy donor-PBMCs. Additionally, we found increased PD-1, CTLA-4, and TIM-3-expressing T cells in MAC- PD individuals in response to MAC-stimulation, indicating that suppressed T cell-mediated response is associated with the susceptibility to MAC infection. These results may help to explain impaired T cell-mediated responses and pave the way for better strategies to achieve protective immunity against MAC infection. View Full-Text
Keywords: nontuberculous mycobacteria; Mycobacterium avium complex; Mycobacterium avium; Mycobacterium intracellulare; CD4+ T cells; immunophenotype nontuberculous mycobacteria; Mycobacterium avium complex; Mycobacterium avium; Mycobacterium intracellulare; CD4+ T cells; immunophenotype
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Han, S.A.; Ko, Y.; Shin, S.J.; Jhun, B.W. Characteristics of Circulating CD4+ T Cell Subsets in Patients with Mycobacterium avium Complex Pulmonary Disease. J. Clin. Med. 2020, 9, 1331.

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