CD137表达和信号功能驱动类的 γδ T 细胞效应器功能,抑制细胞内M.结核病的生长
Xuejiao Ji1, Guixian Huang1, Ying Peng1
1Shanghai Clinical Research Center for Infectious Disease (tuberculosis), Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Institute for Advanced Study, Tongji University School of Medicine, Shanghai, China.
Clinical immunology (Orlando, Fla.)
|July 27, 2024
概括
协同激活信号,如CD137,使Vγ2Vδ2 T细胞能够通过增强效应器功能和抑制Mycobacterium tuberculosis (Mtb) 的生长来对抗结核病 (TB). 活性结核病破坏了这种关键的CD137介导免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 细胞生物学 细胞生物学
背景情况:
- 抗原特异性 γδ T 细胞在免疫中发挥作用,但诱导和维持其效应器功能的协同激活信号尚未完全理解.
- 导致结核病 (TB) 的结核菌菌 (Mtb) 感染构成了全球重大卫生挑战,需要新的治疗点.
- Vγ2Vδ2 T 细胞是人类 γδ T 细胞的主要子集,以它们对 Mtb 抗原的快速反应而闻名.
研究的目的:
- 识别和描述诱导和维持抗原特异性 γδ T 细胞对抗 Mtb. 抗原特异性 γδ T 细胞的 pleiotropic 作用因子功能的联合激活信号.
- 调查CD137信号传递在结核病期间Vγ2Vδ2 T细胞反应中的作用.
- 探索CD137表达Vγ2Vδ2 T细胞在控制Mtb感染中的治疗潜力.
主要方法:
- 在结核素皮肤检测后,分析了耐结核病和活跃结核病患者的Vγ2Vδ2 T细胞上的CD137和CD107a表达.
- 在体外实验中使用抗CD137激素抗体来评估对Vγ2Vδ2 T细胞功能的影响.
- 用Mtb抗原HMBPP刺激Vγ2Vδ2T细胞,评估CD137表达,细胞因子产生和巨细胞中的细胞内Mtb抑制.
- CD137+和CD137-Vγ2Vδ2 T细胞子集的表型和功能特征.
- 人类CD137+ Vγ2Vδ2 T细胞通过收养转移到感染Mtb的SCID小鼠中.
主要成果:
- 结核素的使用诱导了TB耐药个体的Vγ2Vδ2T细胞上的CD137和CD107a表达,而不是活跃的TB患者.
- 抗CD137抗体治疗增强了Vγ2Vδ2 T细胞细胞因子的产生和巨细胞中的Mtb抑制.
- Mtb抗原HMBPP刺激导致未感染个体的Vγ2Vδ2T细胞中持续的CD137表达,与中央记忆表型相关,并增强了增殖反应.
- CD137+ Vγ2Vδ2 T细胞通过非正规的NF-κB通路分化为更多的效应细胞,通过非正规的NF-κB通路产生抗Mtb细胞因子.
- CD137表达标志着抗Mtb效应器功能,导致细胞内Mtb生长抑制,这在活跃的结核病中被破坏.
- CD137+ Vγ2Vδ2 T细胞显示表观遗传驱动的GM-CSF表达,对于控制Mtb生长至关重要.
- 来自CD137+ Vγ2Vδ2 T细胞的外基因组抑制了细胞内Mtb的生长,而这些细胞的采用转移在小鼠中给予了保护.
结论:
- CD137表达和信号传递是抑制细胞内Mtb生长的类 γδT细胞效应因子功能的关键驱动因素.
- 活动性结核病破坏了Vγ2Vδ2 T细胞的CD137介导的抗Mtb功效器功能.
- CD137+ Vγ2Vδ2 T细胞代表了一种有前途的细胞治疗策略,用于控制Mtb感染.
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