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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 Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool.

Author information

1
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
2
Department of Pediatrics, Columbia University, New York, NY 10032, USA.
3
Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
4
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Microbiology & Immunology, Columbia University, New York, NY 10032, USA.
5
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Surgery, Columbia University, New York, NY 10032, USA.
6
Center for Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, New York, NY 10032, USA.
7
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Microbiology & Immunology, Columbia University, New York, NY 10032, USA; Department of Surgery, Columbia University, New York, NY 10032, USA.
8
Department of Surgery, Columbia University, New York, NY 10032, USA.
9
Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Microbiology & Immunology, Columbia University, New York, NY 10032, USA; Department of Surgery, Columbia University, New York, NY 10032, USA. Electronic address: megan.sykes@columbia.edu.

Abstract

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.

KEYWORDS:

T cell receptor; circulating pool; hematopoietic progenitor cell; hematopoietic stem cell; immune tolerance; intestinal allograft; intestinal transplantation; mixed chimerism; recent thymic immigrants; recipient repopulation

PMID:
30503142
PMCID:
PMC6398344
[Available on 2020-02-07]
DOI:
10.1016/j.stem.2018.11.007

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