Skip to main content

Advertisement

Log in

Ex vivo enhancement of antigen-presenting firnction of dendritic cells and its application for DC-based immunotherapy

  • Feature … Practice of Immuno-Cell Therapy and its Future Prospect …
  • Published:
Human Cell Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Dendritic cells (DCs) are potent antigen presenting cells that are able to initiate and modulate immune responses and are hence exploited as cellular vaccines for immunotherapy. In particular DCs generated from peripheral blood monocytes (Mo-DCs) have been used with promising results as a new approach for the immunotherapy of cancer. In this study, we have analyzed the changes in the pattern of expression molecules on Mo-DCs during DC maturation using different maturation cytokine combinations and the expansion capacity of an antigen specific CD+T cells monitored by flow cytometry with the fluorescent tetramers and anti-CD8 monoclonal antibody. These analyses revealed that the expansion of antigen specific CD8+T cells is the most effective when T cells were activated by fully maturated DCs by culturing monocytes for 5 days in the presence of GM-CSF and IL-4, followed by 2–3 days of maturation with pro-inflammatory mediators including TNFα, IL-6, IL-1β and PGE2. These results pave the way to a more effective immunotherapy using DCs for patients with malignancy, as well as infectious diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hart DN: Dendritic cells: unique leukocyte populations which control the primary response. Blood 90: 3245–3287, J. 1997.

    PubMed  CAS  Google Scholar 

  2. Banchereau J, and RM Steinman: Dendritic cells and the control of the immunity. Nature 392: 245–252, 1998.

    Article  PubMed  CAS  Google Scholar 

  3. Steinman RM: The dendritic cell system and its role in immunogenecity. Annu. Rev. Immunol. 9, 271–296, 1991.

    Article  PubMed  CAS  Google Scholar 

  4. Cella M, F Sallusto, and A Lanzavecchia: Origin, maturation and antigen presenting function of dendritic cells. Curr. Opin. Immunol. 9:10–16

  5. Sallusto A, 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 down-regulated by tumor necrosis factor α. J. Exp. Med. 179: 1109, 1994. A997.

    Article  PubMed  CAS  Google Scholar 

  6. Romani N, D Reider, M Heuer, et al.: Generation of mature dendritic cells from human blood: an improved method with special regard to clinical applicability. J. Immunol. Methods 196: 137, 1996.

    Article  PubMed  CAS  Google Scholar 

  7. Caux C, B Vanbervliet, C Massacrier, et.al.: CD34+ hematopoietic progenitors from human cord blood differentiation along two independent dendritic cell pathways in response to GM-CSF+TNF-α J. Exp. Med. 184: 695: 1996.

    Article  PubMed  CAS  Google Scholar 

  8. Girolomoni G, and P Ricciardi-Castagnoli: Dendritic cell hold promise for immunotherapy. Immuno. Today 18: 102, 1997.

    CAS  Google Scholar 

  9. Shortman K, and C Caux: Dendritic cell development: multiple pathways to nature’s adjuvant. Stem Cells 15: 409, 1997.

    Article  PubMed  CAS  Google Scholar 

  10. Zhou JJ, and TF Tedder: CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc. Natl. Acad. Sci. USA 93: 2588, 1996.

    Article  PubMed  CAS  Google Scholar 

  11. Jonuleit H, U Kuhn, G Muller, et al.: 1997. Pro-inflammatroy cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf cerum-free conditions. Eur. J. Immunol. 27: 3135–3241, 1996.

    Article  Google Scholar 

  12. Rajiv Khanna, Scott Bell, Martinal Sherritt, et al.: Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease. Proc. Natl. Acad. Sci. USA, 96: 10391–10396, 1999.

    Article  Google Scholar 

  13. Romero P, Dunbar PR, Valmori D, et al.: Ex vivo staining of metastatic lymph nodes by class I MHC tetramers reveals high numbers of antigen-experienced tumor specific CTL. J.Exp.Med., 188: 1641–1650, 1998.

    Article  PubMed  CAS  Google Scholar 

  14. Valmori D, Fonteneau JF, Maranon Lizana C, et al.: Enhanced generation of specific tumor-reactive CTL in vitro by selected Melan A-/Mart-1 immunodominant peptide analogs. J. Immunol., 160: 1750–1758, 1998.

    PubMed  CAS  Google Scholar 

  15. Springer TA: Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell, 76: 301–314, 1994.

    Article  PubMed  CAS  Google Scholar 

  16. Sallusto F, Palemo B, Lenig D, et al.: Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur J Immunol., 29: 1617–1625, 1999.

    Article  PubMed  CAS  Google Scholar 

  17. Sallusto F, Schaerli P, Loetscher P, et al.: Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur J Immunol., 28: 2760–2769, 1998.

    Article  PubMed  CAS  Google Scholar 

  18. Cyster JG: Chemokines and cell migration in secondary lymphoid organs. Science. 286: 2098–2102, 1999.

    Article  PubMed  CAS  Google Scholar 

  19. Charbonnier AS, Kohrgruber N, Kreihuber E, et al.: Macrophage inflammatory protein 3alpha is involved in the constitutive trafficking of epidermal langerhans cells. J. Exp. Med. 190: 1755–1768, 1999.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mie Nieda.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nieda, M., Tomiyama, M. & Egawa, K. Ex vivo enhancement of antigen-presenting firnction of dendritic cells and its application for DC-based immunotherapy. Hum Cell 16, 199–204 (2003). https://doi.org/10.1111/j.1749-0774.2003.tb00154.x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1111/j.1749-0774.2003.tb00154.x

Key words

Navigation