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 hig h levels of CD34. Using clonal and liquid-culture assays, CD4(+) CD34( ++) Lin(-) (lineage = CD3, CD8, CD10, CD14, CD15, CD16, CD19, CD20, an d glycophorin A) fetal liver progenitors were found to have a greater proliferative potential than CD4(-) CD34(++) Lin(-) progenitors, where as the CD4(-) fraction was more enriched for erythroid progenitors. Bo th 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 sci d/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 mo re frequent than by the CD4(-) fraction when low numbers of cells were injected. These functional data strongly suggest that stem cells resi de among CD4(+) CD34(++) Lin(-) fetal liver cells. This hypothesis was further supported by the observations that CD4(+) CD34(++) Lin(-) fet al liver cells were enriched for CDw90(+) (Thy-1), CD117(+) (kit), CD1 23(+), HLA-DR(+), CD7(-), CD38(-), CD45RA(-), CD71(-), CD115(-) (fms), and rhodamine 123(dull) cells, a phenotypic profile believed to repre sent fetal stem cells. Furthermore, all CD4(+) CD34(++) Lin(-) fetal l iver cells also expressed CD13 and CD33. (C) 1997 by The American Soci ety of Hematology.