title: Fetal liver contains committed NK progenitors, but is not a site for development of CD34+ cells into T cells.
abstract: The presence of T and NK cells in the human fetal liver and the fact that fetal liver hemopoietic progenitor cells develop into T and NK cells suggest a role for the fetal liver compartment in T and NK cell development. In this work, we show that the capacity of fetal liver progenitors to develop into T cells, in a human/mouse fetal thymic organ culture system, is restricted to an immature subset of CD34+ CD38- cells. No T cell-committed precursors are contained within the more differentiated CD34+ CD38+ population. This conclusion is supported by the observations that no TCR-delta gene rearrangements and no pre-TCR-alpha expression can be detected in this population. However, NK cells were derived from CD34+ CD38- and CD34+ CD38+ fetal liver cells cultured in the presence of IL-15, IL-7, and Flt-3 ligand. Eighty to ninety percent of cells arising from the CD34+ CD38+ population expressed the NK cell-associated markers CD56, CD16, CD94, and NKR-P1A. Several subpopulations of NK cell precursors were identified by differential expression of these receptors. Based on the detection of populations with a similar antigenic profile in freshly isolated fetal liver cells, we propose a model of NK cell differentiation. Collectively, our findings suggest that CD34+ cells differentiate into NK cells, but not into mature T cells, in the human fetal liver.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
authors.forename: A C
authors.initials: AC
authors.lastname: Jaleco
authors.forename: B
authors.initials: B
authors.lastname: Blom
authors.forename: P
authors.initials: P
authors.lastname: Res
authors.forename: K
authors.initials: K
authors.lastname: Weijer
authors.forename: L L
authors.initials: LL
authors.lastname: Lanier
authors.forename: J H
authors.initials: JH
authors.lastname: Phillips
authors.forename: H
authors.initials: H
authors.lastname: Spits
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008099:Liver / Q000166:cytology* / Q000276:immunology; D051379:Mice; D011247:Pregnancy; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D018952:Antigens, CD34