CD34(+)CD38(dim) cells in the human thymus can differentiate into T, natural killer, and dendritic cells but are distinct from pluripotent stem cells

Recently we reported that the human thymus contains a minute population of CD34(+)CD38(dim) cells that do not express the T-cell lineage markers CD2 and CD5. The phenotype of this population resembled that of CD34(+)CD38(dim) cells present in fetal liver, umbilical cord blood, and bone marrow known to be highly enriched for pluripotent hematopoietic stem cells. In this report we tested the hypothesis that the CD34(+)CD38(dim) thymocytes constitute the most primitive hematopoietic cells in the thymus using a combination of phenotypic and functional analyses. It was found that in contrast to CD34(+)CD38(dim) cells from fetal liver and bone marrow, CD34(+)CD38(dim) cells from the thymus express high levels of CD45RA and are negative for Thy-1. These data indicate that the CD34(+)CD38(dim) thymocytes are distinct from pluripotent stem cells. CD34(+)CD38(dim) thymocytes differentiate into T cells when cocultured with mouse fetal thymic organs. In addition, individual cells in this population can differentiate either to natural killer cells in the presence of stem cell factor (SCF), interleukin-7 (IL-7), and IL-2 or to dendritic cells in the presence of SCF, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha(TNF alpha), indicating that CD34(+)CD38(dim) thymocytes contain multi-potential hematopoietic progenitors. To establish which CD34(+) fetal liver subpopulation contains the cells that migrate to the thymus, we investigated the T-cell-developing potential of CD34(+)CD38(dim) and CD34(+)CD38(+) fetal liver cells and found that the capacity of CD34(+) fetal liver cells to differentiate into T cells is restricted to those cells that are CD38(dim). Collectively, these findings indicate that cells from the CD34(+)CD38(dim) fetal liver cell population migrate to the thymus before upregulating CD38 and committing to the T-cell lineage, (C) 1996 by The American Society of Hematology.