{"title":"An abnormal increase in CD26(-)CD28(-) cytotoxic effector CD4 and CD8 T cell populations in patients with systemic lupus erythematosus.","authors":"Ryo Hatano, Hayato Nakamura, Ayako Yamamoto, Haruna Otsuka, Takumi Itoh, Nao Hosokawa, Jinghui Yu, Sedigheh Ranjbar, Yuta Hasegawa, Tsutomu Sato, Nam H Dang, Kei Ohnuma, Shinji Morimoto, Iwao Sekigawa, Tomonori Ishii, Chikao Morimoto","doi":"10.1093/intimm/dxae062","DOIUrl":null,"url":null,"abstract":"<p><p>CD26 is a human T cell costimulatory molecule as well as a T cell subset marker, and increase of CD26+ T cells in inflamed tissues and peripheral blood has been reported in diverse autoimmune diseases. In contrast, our group has previously shown that levels of circulating CD26+ T cells are decreased in patients with systemic lupus erythematosus (SLE), although the role of reduced CD26 T cell surface expression in SLE pathology remains to be elucidated. In the present study, we conducted CD26-based T cell subset analyses utilizing peripheral blood mononuclear cells from 57 SLE patients and 31 healthy adult volunteers. We show that the increase in CD26(-) T cell population reflects the abnormal expansion of CD26(-)CD28(-) cytotoxic subsets of both CD8 T cells and CD4 T cells in SLE patients. Single cell RNA sequencing analysis of the CD26(-)CD28(-) CD4 and CD8 T cell populations reveals unique characteristics with similarities to natural killer T cells. In addition, the level of CD26(-)CD28(-) T cells is increased in some active stage SLE patients with renal manifestation. Meanwhile, effect of prednisolone treatment on these populations varies from patient to patient, with levels of these cytotoxic effector populations still being elevated in some inactive stage SLE patients. Taken together, our data suggest that analysis of these populations in SLE may be a useful tool to classify this markedly heterogeneous condition.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/intimm/dxae062","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
CD26 is a human T cell costimulatory molecule as well as a T cell subset marker, and increase of CD26+ T cells in inflamed tissues and peripheral blood has been reported in diverse autoimmune diseases. In contrast, our group has previously shown that levels of circulating CD26+ T cells are decreased in patients with systemic lupus erythematosus (SLE), although the role of reduced CD26 T cell surface expression in SLE pathology remains to be elucidated. In the present study, we conducted CD26-based T cell subset analyses utilizing peripheral blood mononuclear cells from 57 SLE patients and 31 healthy adult volunteers. We show that the increase in CD26(-) T cell population reflects the abnormal expansion of CD26(-)CD28(-) cytotoxic subsets of both CD8 T cells and CD4 T cells in SLE patients. Single cell RNA sequencing analysis of the CD26(-)CD28(-) CD4 and CD8 T cell populations reveals unique characteristics with similarities to natural killer T cells. In addition, the level of CD26(-)CD28(-) T cells is increased in some active stage SLE patients with renal manifestation. Meanwhile, effect of prednisolone treatment on these populations varies from patient to patient, with levels of these cytotoxic effector populations still being elevated in some inactive stage SLE patients. Taken together, our data suggest that analysis of these populations in SLE may be a useful tool to classify this markedly heterogeneous condition.
系统性红斑狼疮患者 CD26(-)CD28(-)细胞毒性效应 CD4 和 CD8 T 细胞群异常增加。
CD26 是一种人类 T 细胞共振分子,也是一种 T 细胞亚群标志物,在多种自身免疫性疾病中都有 CD26+ T 细胞在炎症组织和外周血中增加的报道。相比之下,我们的研究小组以前曾发现,系统性红斑狼疮(SLE)患者的循环 CD26+ T 细胞水平降低,但 CD26 T 细胞表面表达减少在系统性红斑狼疮病理学中的作用仍有待阐明。在本研究中,我们利用 57 名系统性红斑狼疮患者和 31 名健康成年志愿者的外周血单核细胞进行了基于 CD26 的 T 细胞亚群分析。我们发现,CD26(-)T 细胞群的增加反映了系统性红斑狼疮患者 CD8 T 细胞和 CD4 T 细胞中 CD26(-)CD28(-)细胞毒性亚群的异常扩张。对CD26(-)CD28(-) CD4和CD8 T细胞群的单细胞RNA测序分析表明,它们具有与自然杀伤T细胞相似的独特特征。此外,在一些有肾脏表现的活动期系统性红斑狼疮患者中,CD26(-)CD28(-)T细胞的水平会升高。同时,泼尼松龙治疗对这些细胞群的影响因人而异,在一些非活动期系统性红斑狼疮患者中,这些细胞毒性效应细胞群的水平仍然升高。总之,我们的数据表明,对系统性红斑狼疮患者的这些细胞毒效应群进行分析,可能是对这一明显异质性疾病进行分类的有用工具。
期刊介绍:
International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.