共同γ链受体细胞因子诱导人CD8+CD28-T抑制细胞体外扩增及其抗原特异性调节作用

How to harvest enough Regulatory/Suppressor T cells (Treg/Ts) cells in limited time in vitro and assess their stability in vivo are the mail obstacles for Treg/Ts based immunotherapy translating to clinical use. Recently, The proposer found that human purified CD8+ T cells driven by common γ chain cytokines IL-2, IL-7 and IL-15, stimulated by allogeneic antigen presenting cells (APCs), can yield large amounts of allospecific CD8+CD28- T suppressor cells (Ts) in a short time course.But the mechanisms of the expansion system need to be dlucidated,the stability of the CD8+CD28-Ts in vivo need to be assessed. So, in this project, we want to further optimize the new method for expansion of human CD8+CD28- Ts in vitro, elucidate the effect and mechanism of different gamma chain cytokines in generation and amplification of human CD8+CD28- Ts in vitro. By using SCID mice (severe combined immunodeficiency mice, T and B cell-deficient) in vivo experiments, the stability of allospecific suppression of human CD8+CD28- Ts amplificated in vitro will be evaluated. This project could set up an optimized new method for the expansion of human CD8+CD28-Ts in vivo, provide a key technique for further research of human CD8+CD28-Ts,reveal the immune characteristics and allospecific regulation mechanism based on CD8+CD28-Ts. It might hold promise for clinical application in CD8+CD28-Ts cell-based immunotherapy for tolerance induction in transplantation in the future.

如何在体外短时间内获得足够数量的人抗原特异性调节/抑制性T细胞，并验证其在体内环境的稳定性，是基于调节/抑制性T细胞的移植耐受诱导方案转化至临床所面临的主要困难。申请者最近研究通过联合应用共同γ链受体细胞因子，在短时间内大量扩增出具有供者抗原特异性的人CD8+CD28-T抑制细胞（Ts），但扩增体系的具体机制仍不明确，体内稳定性有待评估。我们设想通过阐明不同γ链受体细胞因子在人CD8+CD28-Ts细胞产生和扩增中的作用和机制，进一步优化体外扩增人CD8+CD28-Ts的新方法；通过SCID小鼠体内实验，评价体外扩增的人CD8+CD28-Ts在体内的稳定性和效应。其意义在于：为人CD8+CD28-Ts的增殖微环境和免疫特性的深入研究解决关键技术难题；揭示以人CD8+CD28-Ts为靶点的抗原特异性免疫调节机制；为基于人CD8+CD28-Ts的诱导移植免疫耐受治疗提供新的策略与手段。