Department of Surgery, University of California, San Francisco, California 94143-0780, USA.
Curr Opin Organ Transplant. 2012 Aug;17(4):349-54. doi: 10.1097/MOT.0b013e328355a992.
As regulatory T-cell (Treg) therapy begins to enter the clinic and more clinical trials of Treg therapy are being actively planned for solid organ transplantations, a thorough quantitative assessment of therapeutic dosing is essential for the design of an effective Treg-therapy trial in the solid organ transplant setting.
Considering the requirement for a high percentage of Tregs to control transplant rejection in mouse models of transplantation and the total cellularity of the human T-cell compartment, we estimate that it would take billions of Tregs, preferably alloantigen-reactive Tregs, to effectively control transplant rejection in humans. Donor dendritic cells and B cells can be used to selectively expand donor alloantigen-reactive Tregs. Recent improvements in manufacturing alloantigen-reactive Tregs demonstrate that billions of alloantigen-reactive T cells can be manufactured in short-term cultures.
It is feasible to grow human alloantigen-reactive Tregs up to billions, an optimal number to achieve therapeutic efficacy. Better understanding of Treg lineage commitment and further technological investments are needed to ease the implementation and ensure consistency in Treg manufacturing.
随着调节性 T 细胞（Treg）治疗开始进入临床，并且针对实体器官移植的 Treg 治疗的更多临床试验正在积极规划中，对治疗剂量进行彻底的定量评估对于在实体器官移植环境中设计有效的 Treg 治疗试验至关重要。
考虑到在移植的小鼠模型中需要高比例的 Tregs 来控制移植排斥反应，以及人类 T 细胞区室的总细胞数，我们估计，需要数十亿个 Tregs，最好是同种异体抗原反应性 Tregs，才能有效地控制人类的移植排斥反应。供体树突状细胞和 B 细胞可用于选择性扩增供体同种异体抗原反应性 Tregs。最近在同种异体抗原反应性 Treg 制造方面的改进表明，可以在短期培养中制造数十亿个同种异体抗原反应性 T 细胞。
生长人类同种异体抗原反应性 Tregs 达到数十亿是可行的，这是实现治疗效果的最佳数量。需要更好地了解 Treg 谱系承诺，并进一步进行技术投资，以简化 Treg 制造的实施并确保一致性。
