估计CD4 T细胞子集增殖和分化对艾滋病毒持续性的贡献
Daniel B Reeves1,2, Charline Bacchus-Souffan3, Mark Fitch4
1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA. dreeves@fredhutch.org.
Nature communications
|October 2, 2023
概括
由于CD4+ T细胞的增殖和分化,艾滋病毒在接受抗逆转录病毒疗法 (ART) 的艾滋病毒感染者 (PWH) 中持续存在. 针对这些机制可能会在ART期间减少HIVDNA.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 数学建模的数学建模
背景情况:
- 在抑制性抗逆转录病毒疗法 (ART) 期间,艾滋病毒的持续性是治愈的主要障碍.
- CD4+ T 细胞内的生理机制与维护HIV储存库有关.
研究的目的:
- 在不同的CD4+T细胞子集中研究HIVDNA和CD4+T细胞周转的纵向动力学.
- 模拟艾滋病毒DNA动态,细胞增殖,分化和病毒持久性之间的相互作用.
主要方法:
- 在37名接受ART治疗的男性PWH中,对HIVDNA和细胞循环率的纵向测量.
- 对五种CD4+T细胞子集的分析:原始 (TN),干细胞- (TSCM),中心- (TCM),过渡- (TTM) 和效应记忆 (TEM).
- 开发一个数学模型,整合艾滋病毒DNA动力学,细胞周转,增殖和分化.
主要成果:
- 艾滋病毒DNA在过渡性 (TTM) 和效能记忆性 (TEM) CD4+ T细胞中减少,但在差异较小的子集中没有减少.
- 细胞周转率大约是记忆CD4+T细胞中的HIV清除速度的10倍,这表明增殖会产生新的HIVDNA.
- 数学建模表明,通过细胞分化,通过CD4+T细胞子集之间的HIVDNA转移通过细胞分化,通过增殖和细胞通行产生显著的前病毒.
结论:
- 在ART期间的HIV持久性是由CD4+T细胞内的细胞增殖和分化驱动的.
- 观察到,在更多的增殖/分化CD4+T细胞子集中,HIV DNA的清除速度更快.
- 调节细胞增殖和分化是一种潜在的治疗策略,可以在ART期间减少HIVDNA.
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