Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, UK.
Liver Unit, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
J Exp Med. 2020 Sep 7;217(9). doi: 10.1084/jem.20200050.
The human liver contains specialized subsets of mononuclear phagocytes (MNPs) and T cells, but whether these have definitive features of tissue residence (long-term retention, lack of egress) and/or can be replenished from the circulation remains unclear. Here we addressed these questions using HLA-mismatched liver allografts to discriminate the liver-resident (donor) from the infiltrating (recipient) immune composition. Allografts were rapidly infiltrated by recipient leukocytes, which recapitulated the liver myeloid and lymphoid composition, and underwent partial reprogramming with acquisition of CD68/CD206 on MNPs and CD69/CD103 on T cells. The small residual pool of donor cells persisting in allografts for over a decade contained CX3CR1hi/CD163hi/CD206hi Kupffer cells (KCs) and CXCR3hi tissue-resident memory T cells (TRM). CD8+ TRM were found in the local lymph nodes but were not detected egressing into the hepatic vein. Our findings inform organ transplantation and hepatic immunotherapy, revealing remarkably long-lived populations of KCs and TRM in human liver, which can be additionally supplemented by their circulating counterparts.
人的肝脏中含有专门的单核吞噬细胞（MNP）和 T 细胞亚群，但这些细胞是否具有组织驻留（长期保留、缺乏迁出）的明确特征，以及/或是否可以从循环中补充，目前尚不清楚。在这里，我们使用 HLA 错配的肝移植来区分驻留（供体）和浸润（受体）免疫成分，从而解决了这些问题。移植物很快被受体白细胞浸润，这些白细胞重现了肝脏的髓样和淋巴样组成，并通过 MNP 上的 CD68/CD206 和 T 细胞上的 CD69/CD103 的获得，经历了部分重编程。在十多年的时间里，持续存在于移植物中的一小部分供体细胞包含 CX3CR1hi/CD163hi/CD206hi 库普弗细胞（KC）和 CXCR3hi 组织驻留记忆 T 细胞（TRM）。在局部淋巴结中发现了 CD8+TRM，但没有检测到它们从肝静脉中流出。我们的发现为器官移植和肝免疫治疗提供了信息，揭示了人类肝脏中 KC 和 TRM 具有非常长的寿命，并且可以通过其循环对应物进行补充。
