Alloantigen presenting function of normal human CD34+ hematopoietic cells.
The identification of the CD34 molecule, expressed almost exclusively on human hematopoietic stem cells and committed progenitors, and the development of CD34-specific monoclonal antibodies have made procurement of relatively pure populations of CD34+ marrow cells for autologous transplantation feasible. Characterization of the immunogenicity of CD34+ marrow cells may facilitate the design of successful strategies to use these cells for allogeneic transplantation. CD34+ marrow cells from normal volunteers were enriched to greater than 98% purity by immunoaffinity chromatography on column followed by fluorescence-activated cell sorting. Purified CD34+ cells were tested for expression of HLA-DR and other accessory molecules, and function in hematopoietic colony growth and mixed leukocyte culture (MLC) assays. Greater than 95% CD34+ cells were positive for HLA-DR and 74% +/- 10% were highly positive for CD18, the common beta-chain of a leukointegrin family. CD34+/CD18- cells were small, agranular lymphocytes which contained the majority of precursors for colony-forming cells detected in long-term cultures. They produced almost no stimulation of purified T cells from HLA-DR-incompatible individuals in bulk MLC or in limiting dilution assay. In contrast, CD34+/CD18+ cells were large, were enriched for cells forming mixed colonies in short- but not long-term assays, and were capable of stimulating allogeneic T cells. CD86, a natural ligand for the T-cell activation molecule CD28, was coexpressed with CD18 in 6% +/- 3% of CD34+ cells. CD34+/CD86+ cells, but not CD34+/CD86- cells, exhibited strong alloantigen presenting function. Thus, pluripotent hematopoietic activity and alloantigen presenting function are attributes of distinct subsets of CD34+ marrow cells. CD34+/CD18- or CD34+/CD86- cells may be more effective than either the whole CD34+ population or unseparated marrow in engrafting allogeneic recipients and may also facilitate induction of tolerance.
Rondelli
D
D
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Andrews
R G
RG
Hansen
J A
JA
Ryncarz
R
R
Faerber
M A
MA
Anasetti
C
C
D000328:Adult; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D051940:B7-2 Antigen; D001773:Blood Cells / Q000276:immunology; D001854:Bone Marrow Cells; D018821:CD18 Antigens / Q000032:analysis; D018106:CD28 Antigens / Q000276:immunology; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D006684:HLA-DR Antigens / Q000032:analysis / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014181:Transplantation Immunology
D015703:Antigens, CD; D018952:Antigens, CD34; D051940:B7-2 Antigen; D018821:CD18 Antigens; D018106:CD28 Antigens; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D007519:Isoantigens; D008562:Membrane Glycoproteins