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Induction of Dendritic Cell Differentiation by Granulocyte-Macrophage Colony-Stimulating Factor, Stem Cell Factor, and Tumor Necrosis Factor  In Vitro From Lineage Phenotypes-Negative c-kit+ Murine Hematopoietic Progenitor Cells
Yi Zhang,
Naofumi Mukaida,
Jian-bin Wang,
Akihisa Harada,
Mariko Akiyama, and
Kouji Matsushima
From the Department of Pharmacology, Cancer Research Institute, and the Department of Hygiene, School of Medicine, Kanazawa University, Kanazawa, Japan; and the Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, Tokyo, Japan.
To elucidate the capacity of murine early hematopoietic progenitor cells (HPCs) to differentiate into dendritic cells (DCs), lineage phenotypes (Lin)-c-kit+ HPCs were highly purified from either wild-type or tumor necrosis factor (TNF) receptor p55 (TNF-Rp55)-deficient mice. Upon culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF) for 14 days, wild-type mouse Lin-c-kit+ HPCs did not exhibit characteristic features of DC such as sheet-like projections and veil processes. Moreover, these cells expressed a marginal level of DC markers such as DEC-205, CD86, and barely supported allogenic MLR. However, the addition of mouse TNF generated a large number of cells with typical DC morphology, expression of high levels of Ia, DEC-205, CD86, and function of stimulating allogenic MLR. Moreover, a proportion of these mature DCs and thymic DCs expressed Thy-1 mRNA as well as Thy-1 antigen, whereas freshly isolated splenic DCs did not. These results suggested that DCs generated in our culture system phenotypically resemble thymic ones. In contrast, mouse TNF failed to induce TNF-Rp55-deficient mice-derived Lin-c-kit+ HPCs to generate DCs with characteristic morphology, immunophenotype, and accessory function for T cells under the same culture conditions, suggesting a crucial role of TNF-Rp55 in TNF-mediated DC differentiation from HPCs. Interestingly, human TNF, which can bind to mouse TNF-Rp55 but not TNF-Rp75, was incapable to augment DC generation from wild-type mouse Lin-c-kit+ HPCs. Collectively, these results suggest that TNF has a pivotal role in DC generation from murine early HPCs in collaboration with GM-CSF and SCF through the interaction of TNF-Rp55 and TNF-Rp75.
Blood, Vol. 90 No. 12 (December 15), 1997:
pp. 4842-4853
© 1997 by The American Society of Hematology.
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