Fetal liver contains committed NK progenitors, but is not a site for development of CD34+ cells into T cells.
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.
Jaleco
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Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
Blom
B
B
Res
P
P
Weijer
K
K
Lanier
L L
LL
Phillips
J H
JH
Spits
H
H
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
D018952:Antigens, CD34