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Both perforin and FasL are required for optimal CD8 T cell control of autoreactive B cells and autoantibody production in parent-into-F1 lupus mice
Clinical Immunology ( IF 4.5 ) Pub Date : 2018-06-22 , DOI: 10.1016/j.clim.2018.06.007
Kateryna Soloviova 1 , Maksym Puliaiev 1 , Roman Puliaev 1 , Irina Puliaeva 1 , Charles S Via 1
Affiliation  

To test the relative roles of perforin (pfp) vs. FasL in CTL control of autoreactive B cell expansion, we used the parent-into-F1 model of murine graft-vs.–host disease in which donor CD8 CTL prevent lupus like disease by eliminating activated autoreactive B cells. F1 mice receiving either pfp or FasL defective donor T cells exhibited an intermediate short-term phenotype. Pairing of purified normal CD4 T cells with either pfp or FasL defective CD8 T cell subsets resulted in impaired host B cell elimination and mild lupus like disease that was roughly equivalent in the two experimental groups. Thus, in addition to major roles in tumor and intracellular pathogen control, pfp mediated CD8 CTL killing plays a significant role in controlling autoreactive B cell expansion and lupus downregulation that is comparable to that mediated by FasL killing. Importantly, both pathways are required for optimal elimination of activated autoreactive B cells.



中文翻译:


穿孔素和 FasL 都是 F1 狼疮小鼠亲本中自身反应性 B 细胞的最佳 CD8 T 细胞控制和自身抗体产生所必需的



为了测试穿孔素 (pfp) 与 FasL 在 CTL 控制自身反应性 B 细胞扩增中的相对作用,我们使用了小鼠移植物抗宿主疾病的亲本进入 F1 模型,其中供体 CD8 CTL 通过以下方式预防狼疮样疾病:消除激活的自身反应性 B 细胞。接受 pfp 或 FasL 缺陷供体 T 细胞的 F1 小鼠表现出中间短期表型。将纯化的正常 CD4 T 细胞与 pfp 或 FasL 缺陷的 CD8 T 细胞亚群配对会导致宿主 B 细胞消除受损和轻度狼疮样疾病,这在两个实验组中大致相同。因此,除了在肿瘤和细胞内病原体控制中发挥重要作用外,pfp 介导的 CD8 CTL 杀伤在控制自身反应性 B 细胞扩增和狼疮下调方面也发挥着重要作用,这与 FasL 杀伤介导的作用相当。重要的是,这两种途径都是最佳消除激活的自身反应性 B 细胞所必需的。

更新日期:2018-06-22
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