Zhang Yaoxin, Li Wenhui, Ma Kaili, Zhai Jiawei, Jin Yujia, Zhang Lianjun, Chen Cheng
Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Suzhou Institute of Systems Medicine, Suzhou Jiangsu, 215123 China.
Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Suzhou Institute of Systems Medicine, Suzhou Jiangsu, 215123 China.
Immunol Lett. 2022 May;245:61-68. doi: 10.1016/j.imlet.2022.04.003. Epub 2022 Apr 13.
Highly coordinated signaling following TCR stimulation triggers activation and subsequent differentiation of T cells. CD38 is a major mammalian nicotinamide adenine dinucleotide (NAD) glycohydrolase expressed on T cells, and appears to be an important modulator of T cell response in tumor models. However, the functional involvement of CD38 in T cells remains largely unknown. Therefore, we characterize the presence and function of CD38 in lymphocytes from metastatic pleural effusions (MPE). Of note, a significant accumulation of CD38CD8 T cells was observed in MPE compared with matched peripheral blood mononuclear cells (PBMC). Moreover, PD-1 expression was significantly increased within the CD38CD8 T cell fraction compared to CD38 counterparts. We further showed decreased amounts of IFNγ and TNFα production together with reduced mitochondrial membrane potential in CD38CD8 T cells. Indeed, the impaired capacity of secreting IFNγ and TNFα by CD38CD8 T cells was likely due to damaged mitochondrial function. Taken together, we have identified a subset of CD38CD8 T cells in MPE, which possessed exhausted phenotype accompanied by altered mitochondrial metabolism.
TCR刺激后高度协调的信号传导触发T细胞的激活及随后的分化。CD38是一种在T细胞上表达的主要哺乳动物烟酰胺腺嘌呤二核苷酸（NAD）糖水解酶，在肿瘤模型中似乎是T细胞反应的重要调节因子。然而，CD38在T细胞中的功能作用仍 largely未知。因此，我们对来自转移性胸腔积液（MPE）的淋巴细胞中CD38的存在和功能进行了表征。值得注意的是，与匹配的外周血单个核细胞（PBMC）相比，在MPE中观察到CD38⁺CD8⁺ T细胞显著积聚。此外，与CD38⁻对应物相比，CD38⁺CD8⁺ T细胞亚群内PD-1表达显著增加。我们进一步表明，CD38⁺CD8⁺ T细胞中IFNγ和TNFα的产生量减少，同时线粒体膜电位降低。事实上，CD38⁺CD8⁺ T细胞分泌IFNγ和TNFα的能力受损可能是由于线粒体功能受损。综上所述，我们在MPE中鉴定出了一个CD38⁺CD8⁺ T细胞亚群，其具有耗竭表型并伴有线粒体代谢改变。
