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Expression of CD4 by human hematopoietic progenitors [see comments]
F Louache, N Debili, A Marandin, L Coulombel and W Vainchenker
INSERM U 362, Institut Gustave Roussy, Villejuif, France.
It has been recently reported that murine hematopoietic stem cells and
progenitors express low levels of CD4. In this study, we have investigated
by phenotypic and functional analysis whether the CD4 molecule was also
present on human hematopoietic progenitors. Unfractionated marrow cells or
immunomagnetic bead-purified CD34+ cells were analyzed by two-color
fluorescence with an anti-CD4 and an anti- CD34 monoclonal antibody (MoAb).
A large fraction (25% to 50%) of the CD34+ cells was weakly stained by
anti-CD4 antibodies. Moreover, in further experiments analyzing the
expression of CD4 in different subpopulations of CD34+ cells, we found that
CD4 was predominantly expressed in phenotypically primitive cells (CD34+
CD38-/low CD71low Thy-1high, HLA-DR+/low). However, the presence of CD4 was
not restricted to these primitive CD34+ cell subsets and was also detected
in a smaller fraction of more mature CD34+ cells exhibiting differentiation
markers. Among those, subsets with myelo-monocytic markers (CD13, CD33,
CD14, and CD11b) have a higher CD4 expression than the erythroid or
megakaryocytic subsets. In vitro functional analysis of the sorted CD34+
subsets in colony assays and long-term culture- initiating cell (LTC-IC)
assays confirmed that clonogenic progenitors (colony-forming
unit-granulocyte-macrophage, burst-forming unit- erythroid, and
colony-forming unit-megakaryocyte) and LTC-IC were present in the CD4low
population. However, most clonogenic progenitors were recovered in the CD4-
subset, whereas the CD4low fraction was greatly enriched in LTC-IC. In
addition, CD4low LTC-IC generated larger numbers of primitive clonogenic
progenitors than did CD4- LTC-IC. These observations suggest that, in the
progenitor compartment, the CD4 molecule is predominantly expressed on very
early cells. The CD4 molecule present on CD34+ cells appeared identical to
the T-cell molecule because it was recognized by three MoAbs recognizing
different epitopes of the molecule. Furthermore, this CD4 molecule is also
functional because the CD34+ CD4low cells are able to bind the human
immunodeficiency virus (HIV) gp120. This observation might be relevant to
the understanding of the mechanisms of HIV-induced cytopenias.
Volume 84,
Issue 10,
pp. 3344-3355,
11/15/1994
Copyright © 1994 by The American Society of Hematology
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