Interferon Methods and Protocols pp 167-181

Part of the Methods in Molecular Medicine™ book series (MIMM, volume 116)

Type I Interferons as Regulators of the Differentiation/Activation of Human Dendritic Cells

Methods for the Evaluation of IFN-Induced Effects
  • Stefano M. Santini
  • Caterina Lapenta
  • Filippo Belardelli

Abstract

Recent studies have revealed that type I interferons (IFNs) are powerful inducers of the differentiation and activation of dendritic cells (DCs). These findings emphasize the importance of these cytokines in linking innate and adaptive immunity, suggesting that effects of type I IFN on DCs can play a role in the antitumor and antiviral activity observed in some IFN-treated patients. Thus, the evaluation of the effects of IFN on the differentiation/activation of DCs has become an important approach for testing novel biologically important IFN activities, and the description of some reference methods are urgently needed. In this chapter, we describe some methods for testing the effects of IFNs on the differentiation and activation of human DCs from the peripheral blood monocytes and for the characterization of the DCs generated after IFN treatment.

Key Words

IFN dendritic cells differentiation activation immune response antibodies CD8 T lymphocytes SCID mice 

References

  1. 1.
    Le Bon, A., Schiavoni, G., D’Agostino, G., Gresser, I., Belardelli, F., and Tough, D. F. (2001) Type I interferons potently enhance humoral immunity and can promote isotopes switching by stimulating dendritic cells in vivo. Immunity 14, 461–470.PubMedCrossRefGoogle Scholar
  2. 2.
    Proietti, E., Bracci, L., Puzelli, S., Di Pucchio, T., Sestili, P., De Vincenti, E., et al. (2002) Type I IFN as a natural adjuvant for a protective immune response: lessons from the influenza vaccine model. J. Immunol. 169, 375–383.PubMedGoogle Scholar
  3. 3.
    Montoya, M., Schiavoni, G., Mattei, F., Gresser, I., Belardelli, F., Borrow, P., and Tough, D. F. (2002) Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 99, 3263–3271.PubMedCrossRefGoogle Scholar
  4. 4.
    Paquette, R. L., Hsu, N. C., Kiertscher, S. M., Park, A. N., Tran, L., Roth, M. D., et al (1998) Interferon-alpha and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells. J. Leukoc. Biol. 64, 358–367.PubMedGoogle Scholar
  5. 5.
    Santini, S. M., Lapenta, C., Logozzi, M., Parlato, S., Spada, M., Di Pucchio, T., and Belardelli F. (2000) Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J. Exp. Med. 191, 1777–1788.PubMedCrossRefGoogle Scholar
  6. 6.
    Blanco, P., Palucka, A. K., Gill, M., Pascual, V., and Banchereau, J. (2001). Induction of Dendritic Cell Differentiation by IFN-α in Systemic Lupus Erythematosus. Science 294, 1540–1543.PubMedCrossRefGoogle Scholar
  7. 7.
    Parlato, S., Santini S. M., Lapenta, C., Di Pucchio T., Logozzi, M., Spada, M., et al. (2001) Expression of CCR-7, MIP-3beta, and Th-1 chemokines in type I IFN-induced monocyte-derived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities. Blood 98, 3022–3029.PubMedCrossRefGoogle Scholar
  8. 8.
    Buelens, C., Bartholome, E. J., Amraoui, Z., Boutriaux, M., Salmon, I., Thielemans, K., et al. (2002). Interleukin-3 and interferon beta cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties. Blood 99, 993–998.PubMedCrossRefGoogle Scholar
  9. 9.
    Lapenta, C., Santini, S. M., Logozzi, M., Spada, M., Andreotti, M., Di Pucchio, T., et al. (2003) Potent immune response against HIV-1 and protection from virus challenge in hu-PBL-SCID mice immunized with inactivated virus-pulsed dendritic cells generated in the presence of IFN-alpha. J. Exp. Med. 198, 361–367.PubMedCrossRefGoogle Scholar
  10. 10.
    Belardelli, F. and Ferrantini, M. (2002) Cytokines as a link between innate and adaptive antitumor immunity. Trends Immunol. 23, 201–208.PubMedCrossRefGoogle Scholar
  11. 11.
    Santini, S. M., Di Pucchio, T., Lapenta, C., Parlato, S., Logozzi, M., and Belardelli, F. (2002) The natural alliance between type I interferon and dendritic cells and its role in linking innate and adaptive immunity. J. Interferon. Cytokine Res. 22, 1071–1080.PubMedCrossRefGoogle Scholar
  12. 12.
    Santodonato, L., D’Agostino, G., Nisini, R., Mariotti, S., Monque, D. M., Spada, M., et al. (2003) Monocyte-derived dendritic cells generated after a short-term culture with IFN-alpha and granulocyte-macrophage colony-stimulating factor stimulate a potent Epstein-Barr virus-specific CD8+ T cell response. J. Immunol. 170, 5195–5202.PubMedGoogle Scholar
  13. 13.
    Rossio, J. L., Esser, M. T., Suryanarayana, K., Schneider, D. K., Bess, J. W. Jr, Vasquez, G. M., et al. (1998) Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins. J. Virol. 72, 7992–8001.PubMedGoogle Scholar
  14. 14.
    Mosier, D. E., Gulizia, R. J., Baird, S. M., and Wilson, D. B. (1988) Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335, 256–259.PubMedCrossRefGoogle Scholar
  15. 15.
    Bosma, M. J. and Carroll, A. M. (1991) The SCID mouse mutant: definition, characterization, and potential uses. Annu. Rev. Immunol. 9, 323–350.PubMedCrossRefGoogle Scholar
  16. 16.
    Mosier, D. E., Gulizia, R. J., Baird, S. M., Wilson, D. B., Spector, D. H., and Spector, S. A. (1991) Human immunodeficiency virus infection of human-PBL-SCID mice. Science 251, 791–794.PubMedCrossRefGoogle Scholar
  17. 17.
    Rizza, P., Santini, S. M., Logozzi, M. A., Lapenta, C., Sestili, P., Gherardi, G., et al. (1996) T-cell dysfunctions in hu-PBL-SCID mice infected with human immunodeficiency virus (HIV) shortly after reconstitution: in vivo effects of HIV on highly activated human immune cells. J. Virol. 70, 7958–7964.PubMedGoogle Scholar
  18. 18.
    Sato, K., Kawasaki, H., Nagayama, H., Enomoto, M., Morimotom, C., Tadokoro, K., et al. (2000) TGF-beta 1 reciprocally controls chemotaxis of human peripheral blood monocyte-derived dendritic cells via chemokine receptors. J. Immunol. 164, 2285–2295.PubMedGoogle Scholar
  19. 19.
    Sato, K., Kawasaki, H., Nagayama, H., Serizawa, R., Ikeda, J., Morimoto, C., et al. (1999) CC chemokine receptors, CCR-1 and CCR-3, are potentially involved in antigen-presenting cell function of human peripheral blood monocyte-derived dendritic cells. Blood 93, 34–42.PubMedGoogle Scholar
  20. 20.
    Locardi, C., Puddu, P., Ferrantini, M., Parlanti, E., Sestili, P., Varano, F., and Belardelli, F. (1992) Persistent infection of normal mice with human immunodeficiency virus. J. Virol. 66, 1649–1654.PubMedGoogle Scholar
  21. 21.
    Tosi, D., Valenti, R., Cova, A., Sovena, G., Huber, V., Pilla, L., et al. (2004) Role of cross-talk between IFN-alpha-induced monocyte-derived dendritic cells and NK cells in priming CD8+ T cell responses against human tumor antigens. J. Immunol. 172, 5363–5370.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Stefano M. Santini
    • 1
  • Caterina Lapenta
    • 1
  • Filippo Belardelli
    • 1
  1. 1.Department of Cell Biology and NeurosciencesIstituto Superiore di SanitàRomeItaly

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