CD34+CD38dim cells in the human thymus can differentiate into T, natural killer, and dendritic cells but are distinct from pluripotent stem cells

Abstract

Recently we reported that the human thymus contains a minute population of CD34+CD38dim cells that do not express the T-cell lineage markers CD2 and CD5. The phenotype of this population resembled that of CD34+CD38dim 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+CD38dim 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+CD38dim cells from fetal liver and bone marrow, CD34+CD38dim cells from the thymus express high levels of CD45RA and are negative for Thy-1. These data indicate that the CD34+CD38dim thymocytes are distinct from pluripotent stem cells. CD34+CD38dim 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(TNFalpha), indicating that CD34+CD38dim 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+CD38dim 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 CD38dim. Collectively, these findings indicate that cells from the CD34+CD38dim fetal liver cell population migrate to the thymus before upregulating CD38 and ommitting to the T-cell lineage.

Dendritic cell origins: Puzzles and paradoxes

“…As expected, they differentiate in foetal thymic organ culture (FTOC) into T and NK cells. 45 Particularly, NK cells were shown to arise from a CD44 bright population of large cells, which developed after 6 days of culture with IL-7. [45][46][47] Strikingly, DC have been shown to arise from this population of CD44 bright large cells.…”

Flt‐3 Ligand, in Combination with Bovine Granulocyte–Macrophage Colony‐Stimulating Factor and Interleukin‐4, Promotes the Growth of Bovine Bone Marrow Derived Dendritic Cells

“…Bone marrow precursors [12] and peripheral blood CD14 þ cells [13,14] can also be induced to differentiate, in the presence of GM-CSF and IL-4, to cells with the functional and morphological characteristics of DC. Evidence exists that cells of the lymphoid lineage, which are present in both bone marrow and thymus, can also differentiate into DC [15,16]. These DC express lymphoid markers, including CD8␣ [17], and display different functional activities when compared with myeloid-derived DC.…”

The biology and clinical applications of dendritic cells

“…These thymic DC are CD8 þ and express FasL. In humans, a subset of CD34 þ CD38 þ progenitor cells that expresses the pre-B-cell marker CD10 þ may give rise to T, B, NK and dendritic cells but not other myeloid lineages (Galy et al, 1995;Res et al, 1996). Thus thymic DC and thymocytes may derive from a common precursor that migrates to the thymus prior to lineage committment and terminal differentiation.…”