Developmental plasticity allows outside-in immune responses by resident memory T cells
Developmental plasticity allows outside-in immune responses by resident memory T cells
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DOI：
10.1038/s41590-020-0607-7
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发表时间：
2020-02-17
影响因子：
30.5
通讯作者：
Masopust, David
中科院分区：
文献类型：
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作者：
Fonseca, Raissa;Beura, Lalit K.;Masopust, David
中央记忆 T (T-CM) 细胞巡逻淋巴结，并在再刺激时执行常规记忆反应：增殖、迁移和分化为不同的 T 细胞亚群，同时进行自我更新。常驻记忆 T (T-RM) 细胞驻留在单个器官内，与末端效应器共享特性，有助于快速保护宿主。我们观察到重新激活的 T-RM 细胞重新加入循环池。表观遗传学分析表明，T-RM 细胞与传统记忆 T 细胞群密切相关，与最近激活的效应细胞几乎没有相似之处。从小肠上皮分离的完全分化的 T-RM 细胞表现出分化为 T-CM 细胞、效应记忆 T 细胞和记忆 T-RM 细胞的潜力。 Ex-T-RM 细胞，即重新加入循环池的前肠道 T-RM 细胞，在随后的重新激活中遗传性地保持了回归其起源组织的倾向，并且具有增强的再分化为 T-RM 细胞的能力。因此，T-RM 细胞可以重新加入循环，但有利于在需要时重新形成局部 T-RM。组织驻留记忆 (T-RM) 细胞通常稳定地维持在离散的组织或器官中。 Masopust 及其同事表明，T-RM 细胞可以重新进入循环系统，并表现出相当大的可塑性，尽管它们保留了在其起源组织中重建自身的倾向。
Central memory T (T-CM) cells patrol lymph nodes and perform conventional memory responses on restimulation: proliferation, migration and differentiation into diverse T cell subsets while also self-renewing. Resident memory T (T-RM) cells are parked within single organs, share properties with terminal effectors and contribute to rapid host protection. We observed that reactivated T-RM cells rejoined the circulating pool. Epigenetic analyses revealed that T-RM cells align closely with conventional memory T cell populations, bearing little resemblance to recently activated effectors. Fully differentiated T-RM cells isolated from small intestine epithelium exhibited the potential to differentiate into T-CM cells, effector memory T cells and T-RM cells on recall. Ex-T-RM cells, former intestinal T-RM cells that rejoined the circulating pool, heritably maintained a predilection for homing back to their tissue of origin on subsequent reactivation and a heightened capacity to redifferentiate into T-RM cells. Thus, T-RM cells can rejoin the circulation but are advantaged to re-form local T-RM when called on.Tissue-resident memory (T-RM) cells are generally stably maintained in discrete tissues or organs. Masopust and colleagues show that T-RM cells can reenter the circulation, and exhibit considerable plasticity, although they retain a proclivity to reestablish themselves in their tissue of origin.