HUMAN DENDRITIC CELL-DIFFERENTIATION PATHWAY FROM CD34(+) HEMATOPOIETIC PRECURSOR CELLS

The most effective antigen-presenting cells for T lymphocytes are dend ritic cells (DCs), the differentiation pathway of which, however, is i ncompletely characterized. We examined here how DCs differentiated fro m 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 CD13(hi )HLA-DR(hi)CD4(+), half of them were also CD14(+), and less than or eq ual to 10% were CD1a(+). When day-5 sorted CD13(hi)CD1a(-) and CD13(lo ) cells were further cultured, CD1a(+) cells appeared in the already C D13(hi) population, whereas CD13(hi) cells, a minority of which rapidl y became CD1a(+), emerged from the CD13(lo) population. By day 12, sti ll 66% of bulk cells in suspension were CD13(hi), most of which displa yed high forward and side scatters of large granular cells. Half of CD 13(hi) cells were CD1a(+). All CD13(hi) cells expressed to the same ex tent DR, CD4, costimulatory and adhesion molecules, and various amount s of CD14. CD1a(+) cells stimulated allogeneic lymphocytes more than C D13(hi)CD1a(-) cells and, although they were CD14(+), both cell types were nonspecific esterase-negative nonphagocytic cells and were strong er mixed leukocyte reaction stimulators than were their macrophage cou nterparts. Eventually, the percentage of CD1a(+) cells decreased. Howe ver, typical CD1a(+) DCs still emerged in culture of sorted day-12 CD1 3(hi)CD1a(-) cells, and adding interleukin-4 to bulk cultures at that time led to the persistence of the CD1a(+) population while diminishin g CD14 expression. Thus, this system results first in the differentiat ion of CD13(hi) precursors that strongly express DR and CD4, from whic h more mature CD1a(+) DCs continuously differentiate all along the cul ture period. (C) 1996 by The American Society of Hematology.