KU Leuven-University of Leuven, Department of Microbiology, Immunology and Transplantation, Leuven 3000, Belgium.
VIB Center for Brain and Disease Research, Leuven 3000, Belgium.
Sci Immunol. 2021 Jul 23;6(61). doi: 10.1126/sciimmunol.abe4723.
Regulatory T cells (T) are indispensable for the control of immune homeostasis and have clinical potential as a cell therapy for treating autoimmunity. T can lose expression of the lineage-defining Foxp3 transcription factor and acquire effector T cell (T) characteristics, a process referred to as T plasticity. The extent and reversibility of such plasticity during immune responses remain unknown. Here, using a murine genetic fate-mapping system, we show that T stability is maintained even during exposure to a complex microbial/antigenic environment. Furthermore, we demonstrate that the observed plasticity of T after adoptive transfer into a lymphopenic environment is a property limited to only a subset of the T population, with the nonconverting majority of T being resistant to plasticity upon secondary stability challenge. The unstable T fraction is a complex mixture of phenotypically distinct T, enriched for naïve and neuropilin-1-negative T, and includes peripherally induced T and recent thymic emigrant T These results suggest that a "purging" process can be used to purify stable T that are capable of robust fate retention, with potential implications for improving cell transfer therapy.
调节性 T 细胞（T）对于控制免疫稳态是不可或缺的，并且具有作为治疗自身免疫病的细胞治疗的临床潜力。T 细胞可以失去谱系定义性 Foxp3 转录因子的表达，并获得效应 T 细胞（T）特征，这一过程称为 T 细胞可塑性。在免疫反应期间，这种可塑性的程度和可逆性仍然未知。在这里，我们使用一种小鼠遗传谱系追踪系统表明，即使在暴露于复杂的微生物/抗原环境中，T 细胞的稳定性也得以维持。此外，我们证明，在淋巴减少环境中进行过继转移后观察到的 T 细胞的可塑性是仅局限于 T 细胞群体的一个子集的特性，大多数未转化的 T 细胞在二次稳定性挑战时对可塑性具有抗性。不稳定的 T 细胞亚群是表型上明显不同的 T 细胞的复杂混合物，富含幼稚和神经纤毛蛋白-1 阴性 T 细胞，包括外周诱导的 T 细胞和近期胸腺迁出的 T 细胞。这些结果表明，可以使用“清除”过程来纯化具有强大命运保留能力的稳定 T 细胞，这可能对改善细胞转移治疗具有重要意义。
