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Department of Medicine, Division of Oncology, University of Washington, Seattle, Washington 98195 [H. B., M. L. D., S. Ha., J. R. G., M. A. C.], and CellPro Inc., Bothell, Washington 98021 [S. He.]
Dendritic antigen-presenting cells are considered to be the most effective stimulators of T cell immunity. The use of dendritic cells has been proposed to generate therapeutic T cell responses to tumor antigens in cancer patients. One limitation is that the number of dendritic cells in peripheral blood is exceedingly low. Dendritic cells originate from CD34+ hematopoietic progenitor cells (HPC) which are present in the bone marrow and in small numbers in peripheral blood. CD34+ HPC can be mobilized into the peripheral blood by in vivo administration of granulocyte-colony-stimulating factor. The aim of the current study was to determine whether functional dendritic cells could be elicited and grown in vitro from CD34+ HPC derived from bone marrow or granulocyte-colony-stimulating factor-mobilized peripheral blood. Culture of CD34+ HPC with granulocyte-macrophage-colony-stimulating factor and tumor necrosis factor 
yielded a heterogeneous cell population containing cells with typical dendritic morphology. Phenotypic studies demonstrated a loss of the CD34 molecule over 1 week and an increase in cells expressing surface markers associated with dendritic cells, CD1a, CD80 (B7/BB1), CD4, CD14, HLA-DR, and CD64 (Fc
RI). Function was validated in experiments showing that cultured cells could stimulate proliferation of allogeneic CD4+ and CD8+ T lymphocytes. Antigen-presenting capacity was further confirmed in experiments showing that cultured cells could effectively stimulate tetanus toxoid-specific responses and HER-2/neu peptidespecific responses. The derivation and expansion of dendritic cells from cultured bone marrow or granulocyte-colony-stimulating factor-mobilized CD34+ HPC may provide adequate numbers for testing of dendritic cells in clinical studies, such as vaccine and T cell therapy trials.
1 This work has been supported by Deutsche Forschungsgemeinschaft Grant Be1579/11 (H. B.) and NIH Grants R01 CA57851 and 5 R01 CA49850 (S. H., J. R. G., M. A. C.).
2 Berlex Oncology Foundation Fellow. To whom requests for reprints should be addressed, at Division of Oncology (Mailstop: RM-17), 1959 Northeast Pacific Street, Health Science Building BB1321, Seattle, WA 98195.
Received 9/ 6/94. Accepted 1/ 3/95.
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