Development of intraepithelial T lymphocytes in the intestine of irradiated SCID mice by adult liver hematopoietic stem cells from normal mice

J Hepatol. 1999 Apr;30(4):681-8. doi: 10.1016/s0168-8278(99)80200-1.

Abstract

Background/aims: We recently reported the adult mouse liver to contain c-kit+ stem cells that can give rise to multilineage leukocytes. This study was designed to determine whether or not adult mouse liver stem cells can generate intraepithelial T cells in the intestine as well as to examine the possibility that adult liver c-kit+ stem cells originate from the fetal liver.

Methods: Adult liver mononuclear cells, bone marrow (BM) cells, liver c-kit+ cells or bone BM c-kit+ cells of BALB/c mice were i.v. transferred into 4 Gy irradiated CB17/-SCID mice. In other experiments, fetal liver cells from Ly5.1 C57BL/6 mice and T cell depleted adult BM cells from Ly5.2 C57BL/6 mice were simultaneously transferred into irradiated C57BL/6 SCID mice (Ly5.2). At 1 to 8 weeks after cell transfer, the SCID mice were examined.

Results: Not only BM cells and BM c-kit+ cells but also liver mononuclear cells and liver c-kit+ cells reconstituted gamma delta T cells, CD4+ CD8+ double-positive T cells and CD8 alpha+beta- T cells of intestinal intraepithelial lymphocytes of SCID mice. Injection of a mixture of fetal liver cells from Ly5.1 C57BL/6 mice and adult BM cells from Ly5.2 C57BL/6 mice into Ly5.2 C57BL/6 SCID mice induced both Ly5.1 and Ly5.2 T cells, while also generating c-kit+ cells of both Ly5.1 and Ly5.2 origins in the liver.

Conclusions: Adult mouse liver stem cells were able to generate intestinal intraepithelial T cells of the SCID mice, and it is thus suggested that some adult liver stem cells may indeed be derived from the fetal liver.

MeSH terms

  • Animals
  • Bone Marrow Transplantation / immunology*
  • Fetal Tissue Transplantation / immunology*
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / immunology
  • Liver / cytology
  • Liver / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Peyer's Patches / immunology
  • Proto-Oncogene Proteins c-kit / analysis
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / radiation effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / radiation effects
  • Thymus Gland / immunology
  • Whole-Body Irradiation

Substances

  • Proto-Oncogene Proteins c-kit