Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Department of Pediatrics, Columbia University, New York, NY 10032, USA.
Cell Stem Cell. 2019 Feb 7;24(2):227-239.e8. doi: 10.1016/j.stem.2018.11.007. Epub 2018 Nov 29.
Human intestinal transplantation often results in long-term mixed chimerism of donor and recipient blood in transplant patients. We followed the phenotypes of chimeric peripheral blood cells in 21 patients receiving intestinal allografts over 5 years. Donor lymphocyte phenotypes suggested a contribution of hematopoietic stem and progenitor cells (HSPCs) from the graft. Surprisingly, we detected donor-derived HSPCs in intestinal mucosa, Peyer's patches, mesenteric lymph nodes, and liver. Human gut HSPCs are phenotypically similar to bone marrow HSPCs and have multilineage differentiation potential in vitro and in vivo. Analysis of circulating post-transplant donor T cells suggests that they undergo selection in recipient lymphoid organs to acquire immune tolerance. Our longitudinal study of human HSPCs carried in intestinal allografts demonstrates their turnover kinetics and gradual replacement of donor-derived HSPCs from a circulating pool. Thus, we have demonstrated the existence of functioning HSPCs in human intestines with implications for promoting tolerance in transplant recipients.
人类肠移植后，受者的血液中长期存在供者和受者的混合嵌合体。我们对 21 例接受肠移植超过 5 年的患者的嵌合外周血细胞表型进行了随访。供者淋巴细胞表型提示移植物中的造血干细胞和祖细胞（HSPCs）有一定的贡献。令人惊讶的是，我们在肠道黏膜、派尔集合淋巴结、肠系膜淋巴结和肝脏中检测到了供者来源的 HSPCs。人类肠道 HSPCs 在表型上与骨髓 HSPCs 相似，具有体外和体内多谱系分化潜能。对移植后循环供者 T 细胞的分析表明，它们在受者淋巴器官中经历选择，以获得免疫耐受。我们对肠移植中携带的人类 HSPCs 的纵向研究表明，它们的周转动力学和供体来源 HSPCs 从循环池中的逐渐替代。因此，我们已经证明了在人类肠道中存在有功能的 HSPCs，这对促进移植受者的耐受具有重要意义。
