Center for Immunology, Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA.
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.
Nature. 2021 Apr;592(7854):457-462. doi: 10.1038/s41586-021-03351-3. Epub 2021 Mar 17.
In metazoans, specific tasks are relegated to dedicated organs that are established early in development, occupy discrete locations and typically remain fixed in size. The adult immune system arises from a centralized haematopoietic niche that maintains self-renewing potential, and-upon maturation-becomes distributed throughout the body to monitor environmental perturbations, regulate tissue homeostasis and mediate organism-wide defence. Here we examine how immunity is integrated within adult mouse tissues, and address issues of durability, expansibility and contributions to organ cellularity. Focusing on antiviral T cell immunity, we observed durable maintenance of resident memory T cells up to 450 days after infection. Once established, resident T cells did not require the T cell receptor for survival or retention of a poised, effector-like state. Although resident memory indefinitely dominated most mucosal organs, surgical separation of parabiotic mice revealed a tissue-resident provenance for blood-borne effector memory T cells, and circulating memory slowly made substantial contributions to tissue immunity in some organs. After serial immunizations or cohousing with pet-shop mice, we found that in most tissues, tissue pliancy (the capacity of tissues to vary their proportion of immune cells) enables the accretion of tissue-resident memory, without axiomatic erosion of pre-existing antiviral T cell immunity. Extending these findings, we demonstrate that tissue residence and organ pliancy are generalizable aspects that underlie homeostasis of innate and adaptive immunity. The immune system grows commensurate with microbial experience, reaching up to 25% of visceral organ cellularity. Regardless of the location, many populations of white blood cells adopted a tissue-residency program within nonlymphoid organs. Thus, residence-rather than renewal or recirculation-typifies nonlymphoid immune surveillance, and organs serve as pliant storage reservoirs that can accommodate continuous expansion of the cellular immune system throughout life. Although haematopoiesis restores some elements of the immune system, nonlymphoid organs sustain an accrual of durable tissue-autonomous cellular immunity that results in progressive decentralization of organismal immune homeostasis.
在后生动物中，特定的任务被分配给专门的器官，这些器官在早期发育中建立，占据离散的位置，并且通常保持固定的大小。成人免疫系统起源于一个集中的造血龛位，该龛位保持自我更新的潜力，并且在成熟后分布到全身，以监测环境干扰、调节组织内稳态和介导全身防御。在这里，我们研究了免疫系统如何在成年小鼠组织中整合，并解决了耐久性、可扩展性和对器官细胞性的贡献问题。我们专注于抗病毒 T 细胞免疫，观察到感染后高达 450 天的常驻记忆 T 细胞的持久维持。一旦建立，常驻 T 细胞不需要 T 细胞受体来生存或保持一种准备好的、效应样状态。尽管常驻记忆细胞在大多数黏膜器官中无限期地占主导地位，但通过对联体小鼠进行手术分离，我们发现血液来源的效应记忆 T 细胞具有组织驻留的起源，并且循环记忆细胞在一些器官中缓慢地对组织免疫做出实质性贡献。在进行多次免疫接种或与宠物店小鼠共居后，我们发现，在大多数组织中，组织顺应性（组织改变其免疫细胞比例的能力）使组织驻留记忆得以积累，而不会不可避免地侵蚀先前存在的抗病毒 T 细胞免疫。扩展这些发现，我们证明组织驻留和器官顺应性是构成固有和适应性免疫稳态的普遍方面。免疫系统随着微生物经验的增长而增长，达到内脏器官细胞性的 25%。无论位置如何，许多白细胞群体在非淋巴器官中采用了组织驻留程序。因此，驻留而不是更新或再循环是非淋巴免疫监视的典型特征，器官作为可塑的储存库，可以容纳整个生命周期中细胞免疫系统的持续扩张。尽管造血恢复了免疫系统的一些元素，但非淋巴器官维持着持久的组织自主细胞免疫的积累，导致机体免疫稳态的逐渐去中心化。
