Lim Laura, Jonsson Anna Helena
Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Curr Allergy Asthma Rep. 2025 Jul 26;25(1):31. doi: 10.1007/s11882-025-01211-y.
CD8 T cells comprise a large portion of cells in inflamed tissues in many autoimmune diseases, yet their roles in autoimmune pathogenesis have been unclear.
Newer studies have demonstrated that CD8 T cells perform many effector functions that may play a vital role in autoimmune disease pathogenesis. In some autoimmune diseases, such as type 1 diabetes and polymyositis, classical cytotoxic T lymphocytes are thought to play a driving role, but in most tissues affected by autoimmune disease, granzyme K-expressing CD8 T cells are the most abundant. These cells have low cytotoxic potential and instead stimulate nearby cells by releasing cytokines and granzyme K, which can activate complement cascades. Resident memory CD8 T cells are also present in autoimmune tissues, although their roles in pathogenesis are less clear. Foxp3 CD8 T cells exist, but regulatory functions of CD8 T cells extend beyond this population, as CD39 and GzmB expressed by other CD8 T cell subsets can suppress or kill nearby antigen-presenting cells and other pro-inflammatory cells. In this review, we describe CD8 T cell subsets and functions, their associations with human autoimmune diseases, as well as current and in-development treatments that target CD8 T cells.
在许多自身免疫性疾病中,CD8 T细胞在炎症组织细胞中占很大比例,但其在自身免疫发病机制中的作用尚不清楚。
最新研究表明,CD8 T细胞具有多种效应功能,可能在自身免疫性疾病发病机制中起关键作用。在某些自身免疫性疾病中,如1型糖尿病和多发性肌炎,经典的细胞毒性T淋巴细胞被认为起驱动作用,但在大多数受自身免疫性疾病影响的组织中,表达颗粒酶K的CD8 T细胞最为丰富。这些细胞的细胞毒性潜力较低,而是通过释放细胞因子和颗粒酶K来刺激附近细胞,颗粒酶K可激活补体级联反应。自身免疫组织中也存在驻留记忆CD8 T细胞,尽管它们在发病机制中的作用尚不清楚。存在Foxp3+ CD8 T细胞,但CD8 T细胞的调节功能不仅限于此群体,因为其他CD8 T细胞亚群表达的CD39和颗粒酶B可以抑制或杀死附近的抗原呈递细胞和其他促炎细胞。在本综述中,我们描述了CD8 T细胞亚群及其功能、它们与人类自身免疫性疾病的关联,以及针对CD8 T细胞的现有和正在开发的治疗方法。