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Phenotypic and functional evidence for the expression of CD4 by
hematopoietic stem cells isolated from human fetal liver
MO Muench, MG Roncarolo and R Namikawa
Human Immunology Department, DNAX Research Institute, Palo Alto, CA
94304-1104, USA.
Expression of the CD4 antigen was observed on human fetal liver, fetal bone
marrow (BM), and umbilical cord blood progenitors expressing high levels of
CD34. Using clonal and liquid-culture assays, CD4+ CD34++ Lin- (lineage =
CD3, CD8, CD10, CD14, CD15, CD16, CD19, CD20, and glycophorin A) fetal
liver progenitors were found to have a greater proliferative potential than
CD4- CD34++ Lin- progenitors, whereas the CD4- fraction was more enriched
for erythroid progenitors. Both the CD4+ and the CD4- progenitor
subpopulations also gave rise to multilineage engraftment upon
transplantation into human fetal bone fragments, supportive of B-lymphoid
and myeloid growth, or into human fetal thymic fragments, supportive of
T-cell growth, implanted in scid/scid (SCID) mice. However, in SCID-hu mice
transplanted with graded doses of donor cells ranging from 2.0 x 10(2) to
2.0 x 10(4) cells, BM reconstitution by the CD4+ fraction of CD34++ Lin-
cells was more frequent than by the CD4- fraction when low numbers of cells
were injected. These functional data strongly suggest that stem cells
reside among CD4+ CD34++ Lin- fetal liver cells. This hypothesis was
further supported by the observations that CD4+ CD34++ Lin- fetal liver
cells were enriched for CDw90+ (Thy-1), CD117+ (kit), CD123+, HLA-DR+,
CD7-, CD38-, CD45RA-, CD71-, CD115- (fms), and rhodamine 123(dull) cells, a
phenotypic profile believed to represent fetal stem cells. Furthermore, all
CD4+ CD34++ Lin- fetal liver cells also expressed CD13 and CD33.
Volume 89,
Issue 4,
pp. 1364-1375,
02/15/1997
Copyright © 1997 by The American Society of Hematology
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