title: Phenotypic and functional evidence for the expression of CD4 by hematopoietic stem cells isolated from human fetal liver.
abstract: 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.
authors.affiliation: Human Immunology Department, DNAX Research Institute, Palo Alto, CA 94304-1104, USA.
authors.forename: M O
authors.initials: MO
authors.lastname: Muench
authors.forename: M G
authors.initials: MG
authors.lastname: Roncarolo
authors.forename: R
authors.initials: R
authors.lastname: Namikawa
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001853:Bone Marrow / Q000196:embryology; D001854:Bone Marrow Cells; D015704:CD4 Antigens / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D005312:Fetal Blood / Q000166:cytology; D016332:Fetal Tissue Transplantation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D008099:Liver / Q000166:cytology / Q000196:embryology*; D051379:Mice; D016513:Mice, SCID; D011828:Radiation Chimera; D013950:Thymus Gland / Q000637:transplantation; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D015704:CD4 Antigens