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Insulin-Like Growth Factor Type I (IGF-I) Supports Growth of V-relER Dendritic Cell Progenitors

  • Jaime Madruga
  • Nicolás Koritschoner
  • Gabi Stengl
  • Signe Knespel
  • Petr Bartunek
  • Martin Zenke
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 417)

Abstract

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).

Keywords

Dendritic Cell IGFR Expression Human Estrogen Receptor Dendritic Cell Line Dendritic Cell Progenitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Caux, C., C. Dezutter Dambuyant, D. Schmitt, and J. Banchereau. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360: 258–261 (1992).PubMedCrossRefGoogle Scholar
  2. 2.
    Romani, N., S. Gruner, D. Brang, E. Kampgen, A. Lenz, B. Trockenbacher, G. Konwalinka, P.O. Fritsch, R.M. Steinman, and G. Schuler. Proliferating dendritic cell progenitors in human blood. J. Exp. Med. 180: 83–93 (1994)PubMedCrossRefGoogle Scholar
  3. 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
  4. 4.
    Strunk, D., K. Rappersberger, C. Egger, H. Strobl, E. Kromer, A. Elbe, D. Maurer, and G. Stingl. Generation of human dendritic cells/Langerhans cells from circulating CD34+ hematopoietic progenitor cells. Blood 87: 1292–302 (1996)PubMedGoogle Scholar
  5. 5.
    Peters, J.H., R. Gieseler, B. Thiele, and F. Steinbach. Dendritic cells: From ontogenetic orphans to myclomonocytic descendants. Immun. Today 17: 273–278 (1996)PubMedCrossRefGoogle Scholar
  6. 6.
    Paglia, P., G. Girolomoni, F. Robbiati, F. Granucci, and P. Ricciardi Castagnoli. Immortalized dendritic cell line fully competent in antigen presentation initiates primary T cell responses in vivo. J. Exp. Med. 178: 1893–1901 (1993)PubMedCrossRefGoogle Scholar
  7. 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
  8. 8.
    Girolomoni, G., M.B. Lutz. S. Pastore, C.U. Assmann, A. Cavani, and P. Ricciardi Castagnoli. Establishment of a cell line with features of early dendritic cell precursors from fetal mouse skin. Eur: J. Immunol. 25: 2163–2169 (1995)CrossRefGoogle Scholar
  9. 9.
    Lutz, M.B., C.U. Assmann, G. Girolomoni, and P. Ricciardi Castagnoli.. Different cytokines regulate antigen uptake and presentation of a precursor dendritic cell line. Eur: J. Immunol. 26: 586–594 (1996)CrossRefGoogle Scholar
  10. 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. 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
  12. 12.
    Boehmelt, G., J. Madruga, P. Dorfler, K. Briegel, H. Schwarz, P.J. Enrietto, and M. Zenke. Dendritic cell progenitor is transformed by a conditional v-Rel estrogen receptor fusion protein v-ReIER. Cell 80: 341–352 (1995)PubMedCrossRefGoogle Scholar
  13. 13.
    Wilks, A. F., R. R. Kurhan, C. M. Hovens and S. J. Ralph. The application of the polymerase chain reaction to cloning members of the protein tyrosine kinase family. Gene 85: 67–74 (1989)PubMedCrossRefGoogle Scholar
  14. 14.
    Beug, H., P. Steinlein, P. Bartunek, and M. J Hayman. Avian Hematopoietic Cell Culture: In vitro Model Systems to Study Oncogenic Transformation of Hematopoietic Cells. Methods Enzvmol. 254: 41–76 (1995)CrossRefGoogle Scholar
  15. 15.
    Chomczynski, P. and N. Sacchi. Single-step method of RNA Isolation by Acid Guanidinium ThiocyanatcPhenol-Chloroform Extraction. Anal. Biochern. 162: 167–159 (1987)CrossRefGoogle Scholar
  16. 16.
    Koritschoner, N., P. Bartunek, S. Knespel, and M. Zenke. Assessing the gene expression by domain-directed differential display. In preparation.Google Scholar
  17. 17.
    Szabolcs, P., D. Avigan, S. Gezelter, D.H. Ciocon, M.A. Moore, R.M. Steinman, and J.W. Young. Dendritic cells and macrophages can mature independently from a human bone marrow-derived, post-colony-forming unit intermediate. Blood 87: 4520–4530 (1996)PubMedGoogle Scholar
  18. 18.
    Rosenzwajg, M., B. Canque, and J.C. Gluckman. Human dendritic cell differentiation pathway from CD34+ hematopoietic precursor cells. Blood 87: 535–544 (1996)PubMedGoogle Scholar
  19. 19.
    Saraya, K., and C.D. Reid. Stem cell factor and the regulation of dendritic cell production from CD34+ progenitors in bone marrow and cord blood. Br. J. Haematol. 93: 258–264 (1996)PubMedCrossRefGoogle Scholar
  20. 20.
    Santiago Schwarz, F., K. Laky, and S.E. Carsons. Stem cell factor enhances dendritic cell development. Ade. Exp. Med. Biol. 378: 7–11 (1995)CrossRefGoogle Scholar
  21. 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

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Jaime Madruga
    • 1
  • Nicolás Koritschoner
    • 1
  • Gabi Stengl
    • 1
  • Signe Knespel
    • 1
  • Petr Bartunek
    • 1
  • Martin Zenke
    • 1
  1. 1.Max-Delbrück-Center for Molecular MedicineMDCBerlinGermany

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