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衰老的CD8 T效应记忆细胞功能受损,在衰老和疾病中增强,是免疫治疗的障碍
Paolo S Turano1, Elizabeth Akbulut1, Nica Mariz Aquino2
1Rutgers-New Jersey Medical School, Center for Cell Signaling, Department of Microbiology, Biochemistry and Molecular Genetics, 205 South Orange Avenue, Newark, NJ, United States.
衰老的CD8 T效应记忆 (EM) 细胞随着年龄的增长而积累,表现出功能受损,并导致衰老和疾病. 它们的衰老状态限制了免疫治疗的有效性.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- 衰老细胞对健康至关重要,但随着年龄的增长,它们的积累会损害组织平衡.
- 对于消除衰老细胞至关重要的CD8 T细胞,也表现出衰老的衰老标志物.
- 之前的研究表明,人类 CD8 T 细胞在衰老时会发展出衰老特征.
研究的目的:
- 描述人类SA-βGal-表达的CD8 T效应细胞的衰老状态和功能能力.
- 研究衰老的CD8 T细胞在衰老,疾病和对免疫治疗的反应中的作用.
主要方法:
- 人类CD8T细胞的单细胞RNA测序.
- 在CD8 T细胞中分析SA-βGal活性和衰老标志物.
- 功能性测试评估增殖,细胞因子生产和细胞清除.
主要成果:
- 衰老的SA-βGal表达的CD8 T效应器记忆 (EM) 细胞具有独特的转录特征.
- 这些衰老的CD8 TEM细胞表现出受损的增殖,细胞因子的产生,以及清除衰老 stromal 细胞的能力.
- CD8 TEM细胞中的衰老特征在老年人,疾病患者,吸烟者中普遍存在,并且与免疫治疗反应不佳有关.
- T细胞衰老与T细胞衰老不同,并取代T细胞衰老,影响CD8 TEM细胞功能.
结论:
- 衰老状态显著影响CD8 TEM细胞的功能.
- 衰老和功能障碍的CD8 TEM细胞与衰老,与年龄相关的疾病,毒素暴露和免疫疗法的有效性降低有关.
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