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

Background/Aims: We recently reported the adult mouse liver to contain c-ki t(+) stem cells that can give rise to multilineage leukocytes. This study w as designed to determine whether or not adult mouse liver stem cells can ge nerate intraepithelial T cells in the intestine as well as to examine the p ossibility that adult liver c-kit(+) stem cells originate from the fetal li ver. 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 in to 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 C57B L/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 c ells and liver c-kit+ cells reconstituted gamma delta T cells, CD4(+)CD8(+) double-positive T cells and CD alpha(+)beta(-) T cells of intestinal intra epithelial 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 in to 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 som e adult liver stem cells may indeed be derived from the fetal liver.