Enrichment of Interleukin-2-Responsive Natural Killer Progenitors in Human Bone Marrow

Natural killer (NK) cells can be cultured in interleukin-2 (IL-2)–containing medium from selected human bone marrow (BM) cells obtained after the elimination of mature T and NK cells. To isolate and characterize IL-2—responsive NK progenitors in the selected BM cells, we investigated the expression of IL-2 receptors (IL-2R) on these cells. Neither CD25 (IL-2Rα) nor IL-2Rβ antigen was observed on the selected BM cells before culture. However, CD25+cells without detectable levels of IL-2Rβ antigen appeared 24 hours after culture in IL-2-containing medium. Cells were sorted from each fraction of the selected BM cells 24 hours after culture after staining with anti-CD33, anti-CD34, and anti-CD25 monoclonal antibodies. The generation of NK cells (CD3–CD56+cells) and NK activity were observed only from the CD33–/CD34–/CD25+cell fraction after culture in IL-2—containing medium. The frequency of IL-2–responsive NK progenitors relative to the fraction was 1/231 (95% confidence range, 1/156 to 1/289), which corresponded to the frequency relative to the total number of selected BM cells when the frequency relative to the CD33–/CD34–/CD25+cell fraction was converted according to the percentage of these cells in the total number of selected BM cells. These results indicated that IL-2—responsive NK progenitors were enriched in the CD33–/CD34–/CD25+cell fraction.