扩展的临床级NK细胞比初级NK细胞对HCMV感染的效果更强
Qian-Nan Shang1,2, Xing-Xing Yu1,2, Zheng-Li Xu1
1Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University, Beijing, China.
Cellular & molecular immunology
|June 8, 2023
概括
与初级NK细胞相比,体外扩展的自然杀手 (NK) 细胞表现出增强的抗细胞巨乳病毒 (CMV) 功能. 这种扩张策略显示了预防人类CMV (HCMV) 感染后血造细胞干细胞移植 (HSCT) 的前景.
科学领域:
- 免疫学 免疫学 免疫学
- 移植医学 移植医学
- 病毒学 病毒学
背景情况:
- 细胞巨乳病毒 (CMV) 反激活是所有原性造血干细胞移植 (allo-HSCT) 后死亡的重要原因.
- 早期自然杀手 (NK) 细胞的恢复对于控制移植后的人类CMV (HCMV) 感染至关重要.
- 以前的研究表明,体外扩展的NK细胞具有强大的抗白血病活性,但它们对抗HCMV的疗效尚未被证明.
研究的目的:
- 为了比较ex vivo扩大NK细胞与初级NK细胞的抗HCMV功能.
- 评估扩大NK细胞在临床环境中预防和治疗HCMV感染的治疗潜力.
主要方法:
- 在体外评估NK细胞对HCMV感染纤维细胞的细胞毒性和病毒传播抑制.
- 使用HCMV感染的人性化小鼠进行体内研究,以评估NK细胞持久性和病毒清除.
- 对接受采用NK细胞输液的allo-HSCT患者的临床队列的分析.
主要成果:
- 扩张的NK细胞表现出激活受体,化学因受体和粘附分子的优异表达.
- 扩展的NK细胞显示出对HCMV感染细胞的增强细胞毒性,并在体外更好地抑制HCMV复制.
- 在小鼠中注入扩大的NK细胞导致NK细胞持久性的改善和更有效的病毒消除.
- 在一项临床试验中,接受NK细胞输液的患者在HSCT后显示HCMV感染和耐火HCMV感染的发生率显著降低.
结论:
- 与初级NK细胞相比,体外扩展的NK细胞具有增强的抗HCMV功能.
- 扩大NK细胞的采用输注可以改善NK细胞的复合,并减少HCMV合-HSCT后的并发症.
- 扩张的NK细胞代表了一种有前途的治疗策略,用于治疗移植受体中HCMV感染.
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