CD8⁺ tissue resident memory T cells (T_RM cells) are essential for immune defence against pathogens and malignancies, and the molecular processes that lead to T_RM 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_RM cells, and it was therefore long assumed that T_RM cell formation adheres to a ‘local divergence’ model, in which T_RM 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_RM cell lineage, resulting in the generation of a pool of T_RM 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_RM 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 _RM细胞）对于抵抗病原体和恶性肿瘤的免疫防御至关重要，因此导致 T _RM细胞形成的分子过程具有重要的生物医学意义。先前的工作已经证明存在于发炎组织微环境中的信号可以促进记忆前体细胞分化为成熟的 T _RM细胞，因此长期以来一直假设 T _RM细胞的形成遵循“局部分化”模型，其中Ť _RM细胞谱系决定仅在组织内进行。然而，越来越多的工作为“系统分化”模型提供了证据，其中循环 T 细胞已经预先适应以优先产生 T _RM细胞谱系，从而产生 T _RM细胞平衡的 T池淋巴室内的细胞。在这里，我们回顾了支持这种循环 T _RM细胞祖细胞群存在的新证据，讨论了对它们形成的当前见解，并强调了该领域的开放性问题。