Fukushima Yuji, Ueno Ryuji, Minato Nagahiro, Hattori Masakazu
Department of Regulation of Neurocognitive Disorders (Cyn-K Project), Graduate School of Medicine, Kyoto University, 53 Shogoin-Kawahara-cho, Kyoto 606-8507, Japan.
Medical Innovation Center, Graduate School of Medicine, Kyoto University, 53 Shogoin-Kawahara-cho, Kyoto 606-8507, Japan.
Int Immunol. 2025 Feb 4;37(3):143-152. doi: 10.1093/intimm/dxae056.
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+ programmed cell death protein 1 (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 pro-inflammatory 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, as well as autoimmune and chronic inflammatory diseases, and it provides a novel therapeutic clue.
免疫系统中与年龄相关的变化，即免疫衰老，似乎呈现出颇为矛盾的表现形式：适应性免疫能力减弱，慢性炎症（常伴有自身免疫）倾向增加，这可能是多种与年龄相关疾病发生发展的基础。免疫衰老表型与T和B淋巴细胞系中独特淋巴细胞亚群的出现有关。我们报告，在衰老小鼠中，一种T细胞受体（TCR）反应性严重减弱的CD153 + 程序性细胞死亡蛋白1（PD - 1）+ CD4 + T细胞亚群，即衰老相关T（SAT）细胞，与潜在的自身反应性CD30 + B细胞，如自发生发中心B细胞和年龄相关B细胞共同演变。SAT细胞和CD30 + B细胞通过CD153与CD30的反式相互作用以及与TCR复合物的顺式相互作用而相互激活，导致SAT细胞中TCR介导的增殖得以恢复并分泌大量促炎细胞因子，同时CD30 + B细胞被激活并产生自身抗体。除正常衰老外，在包括自身免疫在内的慢性炎症条件下，SAT细胞及其对应的B细胞的发育可能会在淋巴或淋巴外器官的相关组织中显著加速并积累，可能导致疾病的发病机制和病情加重。本综述总结并讨论了在免疫衰老表型以及自身免疫和慢性炎症性疾病背景下对SAT细胞理解的最新进展，并提供了一条新的治疗线索。
