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01.07.2008 | Original Article | Ausgabe 1/2008

International Journal of Hematology 1/2008

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

Zeitschrift:
International Journal of Hematology > Ausgabe 1/2008
Autoren:
Yoshinobu Saito, Yong Mei Guo, Makoto Hirokawa, Kunie Saito, Atsushi Komatsuda, Naoto Takahashi, Masumi Fujishima, Naohito Fujishima, Junsuke Yamashita, Kenichi Sawada
Wichtige Hinweise
Yoshinobu Saito and Yong Mei Guo contributed equally to this work.

Abstract

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.

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