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. (C) 1996 by The American Society of Hematology.