T淋巴细胞体外发育方法的研究进展

T淋巴细胞（简称T细胞）在细胞过继免疫治疗（ACT）中发挥重要作用，利用T细胞体外发育方法可获得来源稳定且获取简便的T细胞，相比从自体或同种异体组织分离得到T细胞的传统方法更有优势。目前T细胞体外发育方法有胎儿胸腺器官培养、重组胸腺器官培养和Notch信号驱动的二维培养三种。其中胎儿胸腺器官培养操作简便，离体胸腺在体外培养即可支持T细胞分化发育至成熟，但完整的胸腺导致培养物维持时间有限、细胞收获困难；重组胸腺器官培养将各类胸腺基质细胞分散再重组构建三维培养环境，在体内外实验中均可支持T细胞成熟，但生物材料和三维环境导致培养物维持时间和细胞产量均受限；Notch信号驱动的二维培养采用人工呈递Notch信号通路配体来驱动T细胞分化发育，培养体系结构简单且稳定，但仅能支持T细胞发育至早期未成熟阶段。本文综述了上述培养方法的研究进展和不足之处，并讨论了T细胞体外发育未来发展的要求和方向，以助力ACT的推广和应用。

Progress on methods of T lymphocyte development in vitro

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 in vitro, 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 in vitro: 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 in vitro, 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 in vitro and in vivo; 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 in vitro, and discusses the existing problems and the future development to facilitate the application of ACT.