Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, USA.
Nat Rev Immunol. 2022 May;22(5):283-293. doi: 10.1038/s41577-021-00590-3. Epub 2021 Sep 3.
CD8 tissue resident memory T cells (T cells) are essential for immune defence against pathogens and malignancies, and the molecular processes that lead to T cell formation are therefore of substantial biomedical interest. Prior work has demonstrated that signals present in the inflamed tissue micro-environment can promote the differentiation of memory precursor cells into mature T cells, and it was therefore long assumed that T cell formation adheres to a 'local divergence' model, in which T cell lineage decisions are exclusively made within the tissue. However, a growing body of work provides evidence for a 'systemic divergence' model, in which circulating T cells already become preconditioned to preferentially give rise to the T cell lineage, resulting in the generation of a pool of T cell-poised T cells within the lymphoid compartment. Here, we review the emerging evidence that supports the existence of such a population of circulating T cell progenitors, discuss current insights into their formation and highlight open questions in the field.
CD8 组织驻留记忆 T 细胞（T 细胞）是抵御病原体和恶性肿瘤免疫防御的关键，因此，导致 T 细胞形成的分子过程具有重要的生物医学意义。先前的研究表明，炎症组织微环境中存在的信号可以促进记忆前体细胞分化为成熟 T 细胞，因此长期以来人们一直认为 T 细胞的形成遵循“局部分歧”模型，即 T 细胞谱系的决定仅在组织内做出。然而，越来越多的工作提供了证据支持“系统分歧”模型，即循环 T 细胞已经预先被条件化，以优先产生 T 细胞谱系，从而在淋巴器官内产生一群 T 细胞预备 T 细胞。在这里，我们回顾了支持循环 T 细胞前体存在的新兴证据，讨论了它们形成的当前见解，并强调了该领域的开放性问题。
