Phenotypic and functional evidence for the expression of CD4 by hematopoietic stem cells isolated from human fetal liver.

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.