Han Sun Ae, Ko Yousang, Shin Sung Jae, Jhun Byung Woo
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 05355, Korea.
J Clin Med. 2020 May 3;9(5):1331. doi: 10.3390/jcm9051331.
Although prevalence of complex pulmonary disease (MAC-PD) is increasing, limited data are available regarding vulnerability to 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 CD4IL-17 T cells decreased, while CD4IL-4 T cells and CD4CD25Foxp3 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.
尽管复杂性肺部疾病（MAC-PD）的患病率在上升，但关于易患复杂性（MAC）感染的数据有限。为了解MAC与宿主免疫相互作用的病理生物学，从免疫表型和MAC-PD中的功能相关性方面了解循环T细胞的特征很重要。我们旨在对MAC-PD患者循环CD4 T细胞的免疫表型、细胞因子谱和免疫抑制受体进行特征分析。我们招募了71名MAC-PD患者和20名对照个体。进行流式细胞术分析以确定T细胞亚群和免疫检查点标志物。使用酶联免疫吸附测定法测定对MAC反应的体外细胞因子产生。与健康供体外周血单个核细胞（PBMC）中的细胞相比，MAC刺激后，MAC-PD个体外周血单个核细胞（PBMC）中CD4 T细胞和CD4IL-17 T细胞的频率降低，而CD4IL-4 T细胞和CD4CD25Foxp3 T细胞增加。此外，我们发现MAC-PD个体中对MAC刺激有反应的表达PD-1、CTLA-4和TIM-3的T细胞增加，表明T细胞介导的反应受抑制与对MAC感染的易感性有关。这些结果可能有助于解释T细胞介导的反应受损，并为实现针对MAC感染的保护性免疫的更好策略铺平道路。
