T细胞耗尽,共刺激和自身免疫和感染的临床结果
Eoin F McKinney1, James C Lee1, David R W Jayne2
11] Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK [2] Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
Nature
|July 1, 2015
概括
在慢性感染期间损害免疫反应的T细胞疲劳,令人惊的是,在自身免疫性疾病中预测了更好的结果. 了解这种免疫细胞行为为自身免疫和炎症性疾病提供了新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 翻译医学是一种翻译医学.
背景情况:
- 在自身免疫和传染病的临床结果显示出显著的患者对患者的变化.
- T细胞疲劳是一种已知的机制,在慢性感染期间抑制免疫反应,促进病原体的持久性.
研究的目的:
- 研究CD8T细胞耗尽特征在慢性感染和自身免疫性疾病临床结果异质性中的作用.
- 探索T细胞枯竭的分子驱动因素及其作为治疗点的潜力.
主要方法:
- 在患有慢性病毒感染和自身免疫性疾病的患者中,分析与CD8T细胞耗尽相关的转录特征.
- 在体外实验中操纵T细胞抗原受体刺激和CD2共刺激在人类CD8T细胞.
- 使用独立数据集和替代标记器对共刺激/耗尽签名进行验证.
主要成果:
- 一个CD8T细胞耗尽的签名与慢性感染中的病毒清除差异相关,但预测自身免疫性疾病的更好的预后.
- 在自身免疫中,强大的CD4 T细胞共刺激与CD8 T细胞耗尽相反.
- 试验室模型证实了抗原受体刺激和CD2共刺激对T细胞疲劳的影响,PD-1信号减少了非疲劳状态.
结论:
- 在各种免疫介导疾病中,T细胞耗尽在确定临床结果方面发挥着关键作用.
- 准T细胞耗尽途径为自身免疫和炎症性疾病提供了一个有前途的治疗策略.
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