Phagocytosis of co-developing neutrophil progenitors by dendritic cells in a culture of human CD34+ cells with granulocyte colony-stimulating factor and tumor necrosis factor-α

摘要

Tumor necrosis factor-α (TNF-α) has been shown to induce the differentiation of CD34+ cells toward dendritic cells (DCs). We have previously shown that DCs are co-generated from human CD34+ cells during erythroid or megakaryocytic differentiation in the presence of TNF-α, and those DCs are able to stimulate autologous T cell proliferation. The aim of this study was to learn whether the co-stimulation of granulocyte colony-stimulating factor (G-CSF) and TNF-α would generate neutrophil progenitors and DCs together from human CD34+ cells, and if this was the case, to clarify the phenotypic and functional characteristics of these DCs. When highly purified human CD34+ cells were cultured for 7 days with G-CSF alone, the generated cells predominantly expressed a granulocyte marker, CD15, and then differentiated into neutrophils after 14 days of culture. The addition of TNF-α with G-CSF markedly decreased the number of CD15+ cells without affecting the total number of cells during 7 days of culture. Almost one third of the generated cells were positive for CD11c and CD123. Furthermore, CD11c+ cells were found to phagocytose CD15+ cells and were able to induce allogeneic, but not autologous, T cell proliferation in the mixed lymphocyte reaction (MLR). On the other hand, the CD11c+ cells generated by TNF-α and cytokines capable of inducing erythroid differentiation were able to stimulate autologous T cells. There was a difference in the expression of CD80, CD83 and CD86 among CD11c+ cells induced by G-CSF plus TNF-α and those generated by interleukin-3, stem cell factor, and erythropoietin plus TNF-α. These results indicate that the co-stimulation of human CD34+ cells with G-CSF and TNF-α induces the phagocytosis of co-developing neutrophil progenitors by DCs, and the stimulatory effects of these DCs on autologous T cells is different from that of DCs generated from CD34+ cells during erythroid differentiation.