多次再刺激的人类带血衍生的Tregs维持稳定表型和抑制功能,并预测它们对自身免疫糖尿病的治疗效果
Yuanjie Bi1, Ran Kong1, Yani Peng1
1National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Hunan Engineering Research Center of Cell Therapy for Diabetes, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
Diabetology & metabolic syndrome
|March 22, 2024
概括
这项研究开发了一种扩展带血中的调节性T细胞 (Tregs) 的方法,供现成使用. 这些发现表明,体外Treg功能可以预测患者的治疗反应,从而实现精准医学.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞疗法细胞疗法
- 再生医学是一种再生医学.
背景情况:
- 调节性T细胞 (Tregs) 对于免疫平衡和调节至关重要.
- 采用Treg转移疗法已经在临床试验中进行了十多年.
- 在生产准备使用的Treg产品和选择合适的患者方面仍然存在挑战.
研究的目的:
- 开发一种体外方法,在不改变其表型或功能的情况下,从带血中扩展现成的Tregs (UCB-Tregs).
- 设计一种策略,精确选择可能从Treg采用转移疗法中受益的患者.
主要方法:
- 用IL-2和拉巴胺素分离和培养了UCB-Tregs,随后使用CD3/CD28dynanebeads进行了再刺激.
- 评估了UCB-Tregs的表型和抑制能力在18天和42天.
- 分析了体外Treg功能和临床指标之间的相关性,以预测体内治疗效果.
主要成果:
- UCB-Tregs实现了显著的扩张 (18天后增长123倍,42天后增长5981倍),并保留了抑制功能.
- 在体外Treg抑制能力与糖尿病持续时间呈负相关性.
- 具有高体外Treg抑制的患者在12个月内表现出更好的治疗反应.
结论:
- 在不影响其关键特征和功能的情况下,UCB-Tregs的大规模扩展是可行的.
- 在体外Treg抑制功能可以预测体内治疗疗效.
- 这种方法有助于开发现成的Treg产品,并为精确治疗患者进行选择.
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