Zhejiang Da Xue Xue Bao Yi Xue Ban. 2022 Aug 1;51(4):491-499. doi: 10.3724/zdxbyxb-2021-0369.
T lymphocytes (T cells) play an important role in adoptive cellular immunotherapy (ACT). T cells can be stably derived and easily obtained by various methods of T cell development , which have more advantages than traditional methods of T cells isolated from autologous or allogeneic tissues. At present, there are mainly three methods for T cell development : fetal thymus organ culture, recombinant thymus organ culture and two-dimensional culture driven by Notch signal. Fetal thymus organ culture is easy to operate, the isolated thymus can support T cell differentiation and development to maturity , but the intact thymus has problems of limited maintenance time and difficulty in cell harvesting. In recombinant thymic organ culture, various thymic stromal cells are dispersed and recombined to construct a three-dimensional culture environment, which can support T cell maturation and ; however, biomaterials and three-dimensional environment may lead to limited culture maintenance time and cell yield. Two-dimensional culture method uses artificial presentation of Notch signaling pathway ligands to drive T cell differentiation and development; the culture architecture is simple and stable, but it can only support T cell development to the early immature stage. This article reviews the research progress of various culture methods of T cell development , and discusses the existing problems and the future development to facilitate the application of ACT.
T 淋巴细胞(T 细胞)在过继细胞免疫治疗(ACT)中发挥着重要作用。T 细胞可以通过 T 细胞发育的各种方法稳定衍生和轻易获得,这些方法比从自体或同种异体组织中分离 T 细胞的传统方法具有更多优势。目前,T 细胞发育主要有三种方法:胎胸腺器官培养、重组胸腺器官培养和 Notch 信号驱动的二维培养。胎胸腺器官培养操作简单,分离的胸腺可以支持 T 细胞分化和发育成熟,但完整的胸腺存在维持时间有限和细胞收获困难的问题。在重组胸腺器官培养中,分散并重组各种胸腺基质细胞,构建三维培养环境,可支持 T 细胞成熟;然而,生物材料和三维环境可能导致培养维持时间和细胞产量有限。二维培养方法使用人工呈现 Notch 信号通路配体来驱动 T 细胞分化和发育;培养结构简单稳定,但只能支持 T 细胞发育到早期未成熟阶段。本文综述了 T 细胞发育的各种培养方法的研究进展,并讨论了存在的问题和未来的发展方向,以促进 ACT 的应用。