Identification of a common developmental pathway for thymic natural killer cells and dendritic cells.
Current data support the notion that the thymus is seeded by a yet uncommitted progenitor cell able to generate T cells, B cells, natural killer (NK) cells, and dendritic cells (DCs). We assess in this report the developmental relationship of DCs and NK cells derived from a small subset of CD34(+) human postnatal thymocytes that, like the earliest precursors in the fetal thymus, display low CD33 surface expression. Culture of these isolated CD34(+) CD33(lo) thymic progenitors with a mixture of cytokines, including interleukin-7 (IL-7), IL-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor, and stem cell factor, results in predominant generation of DCs. However, the addition of IL-2 to the cytokine mixture leads to the simultaneous development of DCs and NK cells. Both developmental pathways progress through a transient population of CD34(+)CD44(bright) CD5(lo/-)CD33(+) large-sized cells, distinct from small-sized T-lineage precursors, that contain bipotential NK/DC progenitors. These data provide evidence of linked pathways of NK cell and DC development from intrathymic precursors and suggest that NK cells and DCs branch off the T lineage through a common intermediate progenitor.
Márquez
C
C
Centro de Biología Molecular "Severo Ochoa," Universidad Autónoma de Madrid, Madrid, Spain.
Trigueros
C
C
Franco
J M
JM
Ramiro
A R
AR
Carrasco
Y R
YR
López-Botet
M
M
Toribio
M L
ML
D018952:Antigens, CD34 / Q000276:immunology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division; D019070:Cell Lineage / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000276:immunology
D018952:Antigens, CD34; D016207:Cytokines