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Expression of CD86 on Human Marrow CD34+ Cells
Identifies Immunocompetent Committed Precursors of Macrophages and
Dendritic Cells
Rita E. Ryncarz and
Claudio Anasetti
From the Division of Clinical Research, Fred Hutchinson Cancer
Research Center, and the Department of Medicine, Division of Oncology,
University of Washington, Seattle, WA.
Macrophages and dendritic cells derive from a hematopoietic stem
cell and the existence of a common committed progenitor has been
hypothesized. We have recently found in normal human marrow a subset of
CD34+ cells that constitutively expresses HLA-DR and low
levels of CD86, a natural ligand for the T cell costimulation receptor
CD28. This CD34+ subset can elicit responses from
allogeneic T cells. In this study, we show that
CD34+/CD86+ cells can also present tetanus
toxoid antigen to memory CD4+ T cells. CD86 is expressed
at low levels in macrophages and high levels in dendritic cells.
Therefore, we have tested the hypothesis that
CD34+/CD86+ cells are the common precursors
of both macrophages and dendritic cells.
CD34+/CD86+ marrow cells cultured in
granulocyte-macrophage colony-stimulating factor (GM-CSF)-generated
macrophages. In contrast, CD34+/CD86 cells
cultured in GM-CSF generated a predominant population of granulocytes.
CD34+/CD86+ cells cultured in GM-CSF plus
tumor necrosis factor- (TNF-) generated almost exclusively
CD1a+/CD83+ dendritic cells. In contrast,
CD34+/CD86 cells cultured in GM-CSF plus
TNF- generated a variety of cell types, including a small population
of dendritic cells. In addition, CD34+/CD86+ cells cultured in granulocyte
colony-stimulating factor failed to generate CD15+
granulocytes. Therefore, CD34+/CD86+ cells
are committed precursors of both macrophages and dendritic cells. The
ontogeny of dendritic cells was recapitulated by stimulation of
CD34+/CD86 cells with TNF- that induced
expression of CD86. Subsequent costimulation of CD86+
cells with GM-CSF plus TNF- lead to expression of CD83 and produced terminal dendritic cell differentiation. Thus, expression of CD86 on
hematopoietic progenitor cells is regulated by TNF- and denotes differentiation towards the macrophage or dendritic cell lineages.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3892-3900
© 1998 by The American Society of Hematology.
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