{"title":"免疫衰老和疾病中的衰老相关 T 细胞。","authors":"Yuji Fukushima, Ryuji Ueno, Nagahiro Minato, Masakazu Hattori","doi":"10.1093/intimm/dxae056","DOIUrl":null,"url":null,"abstract":"<p><p>Age-related changes in the immune system, referred to as immunosenescence, appear to evolve with rather paradoxical manifestations, a diminished adaptive immune capacity, and an increased propensity for chronic inflammation often with autoimmunity, which may underlie the development of diverse disorders with age. Immunosenescent phenotypes are associated with the emergence of unique lymphocyte subpopulations of both T and B lineages. We report that a CD153+ PD-1+ CD4+ T-cell subpopulation with severely attenuated T-cell receptor (TCR)-responsiveness, termed senescence-associated T (SAT) cells, co-evolve with potentially autoreactive CD30+ B cells, such as spontaneous germinal center B cells and age-associated B cells, in aging mice. SAT cells and CD30+ B cells are reciprocally activated with the aid of the interaction of CD153 with CD30 in trans and with the TCR complex in cis, resulting in the restoration of TCR-mediated proliferation and secretion of abundant proinflammatory cytokines in SAT cells and the activation and production of autoantibodies by CD30+ B cells. Besides normal aging, the development of SAT cells coupled with counterpart B cells may be robustly accelerated and accumulated in the relevant tissues of lymphoid or extra-lymphoid organs under chronic inflammatory conditions including autoimmunity and may contribute to the pathogenesis and aggravation of the disorders. This review summarizes and discusses recent advances in the understanding of SAT cells in the contexts of immunosenescent phenotypes, autoimmune and chronic inflammatory diseases and provides a novel therapeutic clue.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Senescence-Associated T cells in Immunosenescence and Diseases.\",\"authors\":\"Yuji Fukushima, Ryuji Ueno, Nagahiro Minato, Masakazu Hattori\",\"doi\":\"10.1093/intimm/dxae056\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Age-related changes in the immune system, referred to as immunosenescence, appear to evolve with rather paradoxical manifestations, a diminished adaptive immune capacity, and an increased propensity for chronic inflammation often with autoimmunity, which may underlie the development of diverse disorders with age. Immunosenescent phenotypes are associated with the emergence of unique lymphocyte subpopulations of both T and B lineages. We report that a CD153+ PD-1+ CD4+ T-cell subpopulation with severely attenuated T-cell receptor (TCR)-responsiveness, termed senescence-associated T (SAT) cells, co-evolve with potentially autoreactive CD30+ B cells, such as spontaneous germinal center B cells and age-associated B cells, in aging mice. SAT cells and CD30+ B cells are reciprocally activated with the aid of the interaction of CD153 with CD30 in trans and with the TCR complex in cis, resulting in the restoration of TCR-mediated proliferation and secretion of abundant proinflammatory cytokines in SAT cells and the activation and production of autoantibodies by CD30+ B cells. Besides normal aging, the development of SAT cells coupled with counterpart B cells may be robustly accelerated and accumulated in the relevant tissues of lymphoid or extra-lymphoid organs under chronic inflammatory conditions including autoimmunity and may contribute to the pathogenesis and aggravation of the disorders. This review summarizes and discusses recent advances in the understanding of SAT cells in the contexts of immunosenescent phenotypes, autoimmune and chronic inflammatory diseases and provides a novel therapeutic clue.</p>\",\"PeriodicalId\":13743,\"journal\":{\"name\":\"International immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-09-25\",\"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/dxae056\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/intimm/dxae056","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
摘要
免疫系统中与年龄有关的变化被称为免疫衰老,这种变化似乎具有相当矛盾的表现,即适应性免疫能力减弱,慢性炎症倾向增加,往往伴有自身免疫,这可能是随着年龄增长出现各种疾病的原因。免疫增强表型与 T 系和 B 系独特淋巴细胞亚群的出现有关。我们报告说,在衰老的小鼠中,一个对 T 细胞受体(TCR)反应性严重减弱的 CD153+ PD-1+ CD4+ T 细胞亚群(称为衰老相关 T 细胞(SAT))与潜在的自反应性 CD30+ B 细胞(如自发生殖中心 B 细胞和年龄相关 B 细胞)共同进化。SAT 细胞和 CD30+ B 细胞借助 CD153 与 CD30 的反式相互作用和与 TCR 复合物的顺式相互作用相互激活,导致 TCR 介导的增殖恢复,SAT 细胞分泌大量促炎细胞因子,CD30+ B 细胞激活并产生自身抗体。除正常衰老外,在慢性炎症(包括自身免疫)条件下,SAT 细胞和对应的 B 细胞可能会在淋巴或淋巴外器官的相关组织中加速发育和积累,并可能导致疾病的发病机制和恶化。这篇综述总结并讨论了在免疫增强表型、自身免疫和慢性炎症疾病背景下了解 SAT 细胞的最新进展,并提供了一条新的治疗线索。
Senescence-Associated T cells in Immunosenescence and Diseases.
Age-related changes in the immune system, referred to as immunosenescence, appear to evolve with rather paradoxical manifestations, a diminished adaptive immune capacity, and an increased propensity for chronic inflammation often with autoimmunity, which may underlie the development of diverse disorders with age. Immunosenescent phenotypes are associated with the emergence of unique lymphocyte subpopulations of both T and B lineages. We report that a CD153+ PD-1+ CD4+ T-cell subpopulation with severely attenuated T-cell receptor (TCR)-responsiveness, termed senescence-associated T (SAT) cells, co-evolve with potentially autoreactive CD30+ B cells, such as spontaneous germinal center B cells and age-associated B cells, in aging mice. SAT cells and CD30+ B cells are reciprocally activated with the aid of the interaction of CD153 with CD30 in trans and with the TCR complex in cis, resulting in the restoration of TCR-mediated proliferation and secretion of abundant proinflammatory cytokines in SAT cells and the activation and production of autoantibodies by CD30+ B cells. Besides normal aging, the development of SAT cells coupled with counterpart B cells may be robustly accelerated and accumulated in the relevant tissues of lymphoid or extra-lymphoid organs under chronic inflammatory conditions including autoimmunity and may contribute to the pathogenesis and aggravation of the disorders. This review summarizes and discusses recent advances in the understanding of SAT cells in the contexts of immunosenescent phenotypes, autoimmune and chronic inflammatory diseases and provides a novel therapeutic clue.
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.