Characterizing the lymphopoietic kinetics and features of hematopoietic progenitors contained in the adult murine liver in vivo

PLoS One. 2013 Oct 9;8(10):e76762. doi: 10.1371/journal.pone.0076762. eCollection 2013.

Abstract

The appearance of donor-derived lymphocytes in liver transplant patients suggests that adult livers may contain cells capable of lymphopoiesis. However, only a few published studies have addressed the lymphopoietic capacity of adult liver cells, and its kinetics and features remain unclear. Herein, we investigated the lymphopoietic capacity of adult liver mononuclear cells (MNCs) and purified liver hematopoietic progenitor cells (HPCs) in vivo. Similar to bone-marrow transplantation (BMT), transplantation of liver MNCs alone was able to rescue survival of lethally irradiated mice. In terms of kinetics, liver MNC-derived myeloid lineage cells reconstituted more slowly than those from BMT. Liver MNC-derived lymphocyte lineage cells in the blood, spleen and BM also reconstituted more slowly than BMT, but lymphocytes in the liver recovered at a similar rate. Interestingly, liver MNCs predominantly gave rise to CD3(+)CD19(-) T cells in both irradiated WT and non-irradiated lymphocyte-deficient Rag-1(-/-)Il2rg(-/-) recipients. To define the lymphopoietic potential of various cell populations within liver MNCs, we transplanted purified lineage-negative (Lin(-)) liver HPCs into recipient mice. Unlike total liver MNCs, liver HPCs reconstituted T and B cells in similar frequencies to BMT. We further determined that the predominance of T cells observed after transplanting total liver MNCs likely originated from mature T cells, as purified donor liver T cells proliferated in the recipients and gave rise to CD8(+) T cells. Thus, the capacity of donor adult liver cells to reconstitute lymphocytes in recipients derives from both HPCs and mature T cells contained in the liver MNC population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Hematopoietic Stem Cells / cytology*
  • Kinetics
  • Liver / cytology*
  • Liver / immunology*
  • Liver Transplantation
  • Lymphopoiesis*
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / cytology

Grants and funding

This work was supported by the Ministry of Science & Technology of China (973 Basic Science Project 2013CB944902) and the Natural Science Foundation of China (#31021061). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.