Insulin-Like Growth Factor Type I (IGF-I) Supports Growth of V-relER Dendritic Cell Progenitors
Over the past few years, several protocols have been established to differentiate antigen-presenting dendritic cells (DC) from DC progenitors grown in vitro (1–4, see also review of Peters et al., 5). While these procedures yield fully competent DC in large numbers, there is also some heterogenity in the cultures obtained since the cell populations are not clonal. Several DC lines were also established (6–10) which however in most instances recapitulate only part of the DC specific phenotype. Recently we have developed an in vitro differentiation system for DC which is based on the conditional hormone-inducible V-relER oncogene (11, 12). V-rel represents a retrovirus-transduced version of crel and is a member of the NF-kB/rel transcription factor family. In the chimeric V-relER gene, V-rel is fused to the hormone-binding domain of the human estrogen receptor, thus making the transforming capacity of V-rel hormone-inducible. Accordingly V-relER is capable of transforming chicken bone marrow cells in the presence of estrogen while it is inactive in the absence of hormone. Most importantly, V-relER transformed bone marrow cells can be grown as clonal homogenous cell populations to large cell numbers and induced to differentiate into DC after experimentally “switching off’ V-relER activity by removing estrogen or by adding the estrogen antagonist ICI 164,384 (12, Fig. 1).
KeywordsDendritic Cell IGFR Expression Human Estrogen Receptor Dendritic Cell Line Dendritic Cell Progenitor
Unable to display preview. Download preview PDF.
- 3.Sallusto, F., and A. Lanzavecchia. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J. Exp. Med. 179: 1109–1118 (1994)PubMedCrossRefGoogle Scholar
- 7.Elbe, A., S. Schleischitz, D. Strunk, and G. Stingl. Fetal skin-derived MHC class 1+, MHC class II- dendritic cells stimulate MHC class I-restricted responses of unprimed CD8+ T cells. J. Immunol. 153 2878–2889(1994)Google Scholar
- 10.Volkmann, A., J. Neefles, and B. Stockinger. A conditional immortalized dendritic cell line which differentiates in contact with T cells or T cell-derived cytokines. In press.Google Scholar
- 11.Boehmelt, G., A. Walker, N. Kabrun, G. Mellitzer, H. Beug, M. Zenke, and P.J. Enrietto. Hormone-regulated v-rel estrogen receptor fusion protein: reversible induction of cell transformation and cellular gene expression. EMBOJ. 11: 4641–52 (1992)Google Scholar
- 16.Koritschoner, N., P. Bartunek, S. Knespel, and M. Zenke. Assessing the gene expression by domain-directed differential display. In preparation.Google Scholar
- 21.Young, J.W., P. Szabolcs, and M.A. Moore. Identification of dendritic cell colony-forming units among normal human CD34+ bone marrow progenitors that are expanded by c-kit-ligand and yield pure dendritic cell colonies in the presence of granulocyte/macrophage colony-stimulating factor and tumor necrosis factor alpha. J. Exp. Med. 182: 1111–1119 (1995)PubMedCrossRefGoogle Scholar