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Human dendritic cell differentiation pathway from CD34+ hematopoietic
precursor cells
M Rosenzwajg, B Canque and JC Gluckman
Laboratoire de Biologie et Genetiques des Deficits Immunitaires, faculte de
Medecine, Paris, France.
The most effective antigen-presenting cells for T lymphocytes are dendritic
cells (DCs), the differentiation pathway of which, however, is incompletely
characterized. We examined here how DCs differentiated from human cord
blood CD34+ progenitor cells cultured with granulocyte- macrophage
colony-stimulating factor, tumor necrosis factor-alpha, and stem cell
factor. After 5 days, 2 of 3 nonadherent cells were CD13hiHLA- DRhiCD4+,
half of them were also CD14+, and < or = 10% were CD1a+. When day-5
sorted CD13hiCD1a- and CD13lo cells were further cultured, CD1a+ cells
appeared in the already CD13hi population, whereas CD13hi cells, a minority
of which rapidly became CD1a+, emerged from the CD13lo population. By day
12, still 66% of bulk cells in suspension were CD13hi, most of which
displayed high forward and side scatters of large granular cells. Half of
CD13hi cells were CD1a+. All CD13hi cells expressed to the same extent DR,
CD4, costimulatory and adhesion molecules, and various amounts of CD14.
CD1a+ cells stimulated allogeneic lymphocytes more than CD13hiCD1a- cells
and, although they were CD14+, both cell types were nonspecific
esterase-negative nonphagocytic cells and were stronger mixed leukocyte
reaction stimulators than were their macrophage counterparts. Eventually,
the percentage of CD1a+ cells decreased. However, typical CD1a+ DCs still
emerged in culture of sorted day-12 CD13hiCD1a- cells, and adding
interleukin-4 to bulk cultures at that time led to the persistence of the
CD1a+ population while diminishing CD14 expression. Thus, this system
results first in the differentiation of CD13hi precursors that strongly
express DR and CD4, from which more mature CD1a+ DCs continuously
differentiate all along the culture period.
Volume 87,
Issue 2,
pp. 535-544,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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