Generation of Mature Dendritic Cells from Human Blood

An Improved Method with Special Regard to Clinical Applicability
  • Gerold Schuler
  • Nikolaus Romani
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 417)


Efficient methods to generate large numbers of dendritic cells have been developed in the past five years. Caux et al.1 have introduced the approach to grow dendritic cells from rare CD34+ progenitor cells in (cord) blood using GM-CSF and TNF-α as the critical cytokines. On the other hand, Sallusto et al.2 and Romani et al.3 have established procedures that make use of the more abundant monocytic CD34-negative and CD14+precursors in peripheral blood. GM-CSF and IL-4 were the necessary cytokines. Both approaches have since been widely used, even up to the stage of clinical trials.


Dendritic Cell Major Histocompatibility Complex Class Immature Dendritic Cell Mature Dendritic Cell Invariant Chain 
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  1. 1.
    Caux, C., C. Dezutter-Dambuyant, D. Schmitt, and J. Banchereau. 1992. GM-CSF and TNF-a cooperate in the generation of dendritic Langerhans cells. Nature 360: 258–261.PubMedCrossRefGoogle Scholar
  2. 2.
    Sallusto, F. and A. Lanzavecchia. 1994. 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 a. J. Exp. Med. 179: 1109–1118.PubMedCrossRefGoogle Scholar
  3. 3.
    Romani, N., S. Gruner, D. Brang, E. Kämpgen, A. Lenz, B. Trockenbacher, G. Konwalinka, P. O. Fritsch, R. M. Steinman, and G. Schuler. 1994. Proliferating dendritic cell progenitors in human blood. J. Exp. Med. 180: 83–93.PubMedCrossRefGoogle Scholar
  4. 4.
    Romani, N., D. Reider, M. Heuer, S. Ebner, E. Kämpgen, B. Eibl, D. Niederwieser, and G. Schuler. 1996. Generation of mature dendritic cells from human blood: An improved method with special regard to clinical applicability. J. lmmunol. Methods 196: 137–151CrossRefGoogle Scholar
  5. 5.
    Bender, A., M. Sapp, G. Schuler, R. M. Steinman, and N. Bhardwaj. 1996. Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood. J. Immunol. Methods 196: 121–135PubMedCrossRefGoogle Scholar
  6. 6.
    Zhou, L.-J. and T. F. Tedder. 1995. Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. J. Immunol. 154: 3821–3835.PubMedGoogle Scholar
  7. 7.
    Sallusto, F., M. Cella, C. Danieli, and A. Lanzavecchia. 1995. Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: Downregulation by cytokines and bacterial products. J. Exp. Med. 182: 389–400.PubMedCrossRefGoogle Scholar
  8. 8.
    Kämpgen, E., N. Koch, F. Koch, P. Stöger, C. Heufler, G. Schuler, and N. Romani. 1991. Class II major histocompatibility complex molecules of murine dendritic cells: Synthesis, sialylation of invariant chain, and antigen processing capacity are down-regulated upon culture. Proc. Natl. Acad. Sci. USA 88: 3014–3018.PubMedCrossRefGoogle Scholar
  9. 9.
    Pure, E., K. Inaba, M. T. Crowley, L. Tardelli, M. D. Witmer-Pack, G. Ruberti, G. Fathman, and R. M. Steinman. 1990. Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain. J. Exp. Med. 172: 1459–1469.PubMedCrossRefGoogle Scholar
  10. 10.
    Becker, D., A. B. Reske-Kunz, J. Knop, and K. Reske. 1991. Biochemical properties of MHC class II molecules endogenously synthesized and expressed by mouse Langerhans cells. Eur. J. Immunol. 21: 12–13CrossRefGoogle Scholar
  11. 11.
    Stössel, H., F. Koch, E. Kämpgen, P. Stöger, A. Lenz, C. Heufler, N. Romani, and G. Schuler. 1990. Disappearance of certain acidic organelles (endosomes and Langerhans cell granules) accompanies loss of antigen processing capacity upon culture of epidermal Langerhans cells. J. Exp. Med. 172: 1471–1482.PubMedCrossRefGoogle Scholar
  12. 12.
    Kleijmeer, M. J., V. M. J. Oorschot, and H. J. Geuze. 1994. Human resident Langerhans cells display h lysosomal compartment enriched in MHC class II. J. Invest. Dermatol. 103: 516–523.PubMedCrossRefGoogle Scholar
  13. 13.
    Radmayr, C., G. Bock, A. Hobisch, H. Klocker, G. Bartsch, and M. Thurnher. 1995. Dendritic antigen-presenting cells from the peripheral blood of renal-cell-carcinoma patients. Int. J. Cancer 63: 627–632.PubMedCrossRefGoogle Scholar
  14. 14.
    Pope, M., M. G. H. Betjes, H. Hirmand, L. Hoffman, and R. M. Steinman. 1995. Both dendritic cells and memory T lymphocytes emigrate from organ cultures of human skin and form distinctive dendritic-T-cell conjugates. J. Invest. Dermatol. 104: 11–17.PubMedCrossRefGoogle Scholar
  15. 15.
    Heufler, C., F. Koch, U. Stanzl, G. Topar, M. Wysocka, G. Trinchieri, A. Enk, R. M. Steinman, N. Romani, and G. Schuler. 1996. Interleukin-12 is produced by dendritic cells and mediates T helper I development as well as interferon-gamma production by T helper 1 cells. Eur.1. Immunol. 26: 659–668.CrossRefGoogle Scholar
  16. 16.
    Macatonia, S. E., N. A. Hosken, M. Litton, P. Vieira, C.-S. Hsieh, J. A. Culpepper, M. Wysocka, G. Trinchieri, K. M. Murphy, and A. O’Garra. 1995. Dendritic cells produce IL-12 and direct the development of Th I cells from naive CD4’ T cells. J. Immunol. 154: 5071–5079.PubMedGoogle Scholar
  17. 17.
    Koch, F., U. Stanzl, P. Jennewein, K. Janke, C. Heufler, E. Kämpgen, N. Romani, and G. Schuler. 1996. High level IL-12 production by murine dendritic cells: Upregulation via MHC class 11 and CD40 molecules and downregulation by IL-4 and IL-10. J. Exp. Med. 184: 741–746.PubMedCrossRefGoogle Scholar
  18. 18.
    Cella, M., D. Scheidegger, K. Palmer-Lehmann, P. Lane, A. Lanzavecchia, and G. Alber. 1996. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J. Exp. Med. 184: 747–752.PubMedCrossRefGoogle Scholar
  19. 19.
    Shu, U., M. Kiniwa, C. Y. Wu, C. Maliszewski, N. Vezzio, J. Hakimi, M. Gately, and G. Delespesse. 1995. Activated T cells induce interleukin-12 production by monocytes via CD40–CD40ligand interaction. Eur J. Immunol. 25: 1125–1128.PubMedCrossRefGoogle Scholar
  20. 20.
    Dummer, W., B. C. Bastian, N. Ernst. C. Schänzle, A. Schwaaf, and E. B. Bröcker. 1996. Interleukin-10 production in malignant melanoma: Preferential detection of IL-10-secreting tumor cells in metastatic lesions. Int. J. Cancer 66: 607–610.PubMedCrossRefGoogle Scholar
  21. 21.
    Buelens, C., F. Willems, A. Delvaux, G. Piérard, J. P. Delville, T. Velu, and M. Goldman. 1995. Interleukin10 differentially regulates B7–1 (CD80) and B7–2 (CD86) expression on human peripheral blood dendritic cells. Eur J. Immunol. 25: 2668–2672.PubMedCrossRefGoogle Scholar
  22. 22.
    Péguet-Navarro, J., C. Mouton, C. Caux. C. Dalbiez-Gauthier, J. Banchereau, and D. Schmitt. 1994. Interleukin-10 inhibits the primary allogeneic T cell response to human epidermal Langerhans cells. Eur J. In, munol. 24: 884–891.Google Scholar
  23. 23.
    Austyn, J. M. 1996. New insights into the mobilization and phagocytic activity of dendritic cells. J. Exp. Med. 183: 1287–1292.PubMedCrossRefGoogle Scholar
  24. 24.
    Lukas, M., H. Stössel, L. Hefel, S. Imamura, P. Fritsch, N. T. Sepp, G. Schuler, and N. Romani. 1996. Human cutaneous dendritic cells migrate through dermal lymphatic vessel culture model. J. Invest. Dermatol. 106: 1293–1299.PubMedCrossRefGoogle Scholar
  25. 25.
    Hsu, F. J., C. Benike, F. Fagnoni, T. M. Liles, D. Czerwinski, B. Taidi, E. G. Engleman, and R. Levy. 1996. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med. 2: 52–58.PubMedCrossRefGoogle Scholar
  26. 26.
    Zhou, L. J. and T. F. Tedder. 1996. CD14` blood monocytes can differentiate into functionally mature CD83 dendritic cells. Proc. Natl. Acad. Sci. USA 93: 2588–2592.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Gerold Schuler
    • 1
  • Nikolaus Romani
    • 2
  1. 1.Department of DermatologyUniversity of Erlangen-NürnbergErlangenGermany
  2. 2.Department of DermatologyUniversity of InnsbruckInnsbruckAustria

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