FUNCTIONAL DIFFERENCES BETWEEN SUBPOPULATIONS OF MOBILIZED PERIPHERALBLOOD-DERIVED CD34(-DR, CD33, CD38 AND C-KIT ANTIGENS() CELLS EXPRESSING DIFFERENT LEVELS OF HLA)

We have investigated the functional characteristics of peripheral bloo d-derived CD34(+) cells mobilized by a combination of chemotherapy and G-CSF (mobilized peripheral blood-derived [MPB] CD34(+) cells). In th is study, subpopulations of MPB CD34(+) cells have been directly compa red in clonal cultures, long-term cultures with bone marrow (BM) strom al cells, and single-cell cultures. MPB CD34(+) cells could be subdivi ded by expression levels of HLA-DR (DR), CD38, CD33 and c-kit antigens . The majority of MPB CD34(+) cells expressed DR and CD38 antigens. In contrast, approximately 60% and 20% of the MPB CD34(+) cells expresse d CD33 and c-kit antigens, respectively. Interestingly, MPB CD34(+) ce lls can be subdivided into three fractions which express high, low or negative levels of c-kit receptor. All types of committed progenitors were observed in populations of CD34(+)DR(+), CD34(+)DR(-), CD34(+)CD3 3(-), CD34(+)CD38(+) and CD34(+) c-kit(low) cells. Colony forming unit -granulocyte/macrophage was highly enriched in the population of CD34( +)CD33(+) cells, whereas BFU-E was highly enriched in the population o f CD34(+) C-kit(high) cells. In the population of CD34(+)CD38(-) cells , however, a few myeloid progenitors were detected. In addition, limit ing dilution analyses clearly showed that the long-term culture-initia ting cell (LTC-IC) is enriched in the populations of CD34(+)DR(-), CD3 4(+)CD33(-) and CD34(+)c-kit(- or low) cells, but very few in CD34(+) c-kit(high) cells, and that CD38 antigen is not a useful marker for th e enrichment of LTC-IC derived from MPB CD34(+) cells. Moreover, singl e cell clone sorting experiments clearly demonstrated the functional d ifferences between CD34(+)CD38(+) and CD34(+)CD38(-) cells as well as CD34(+) cells expressing different levels of c-kit receptor. Our resul ts suggest that an immunophenotype of LTC-IC is different between BM-, cord blood- and MPB-derived CD34(+) cells and that primitive and comm itted progenitors existing in these sources may be functionally differ ent.