Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

A dendritic-cell-derived C–C chemokine that preferentially attracts naive T cells

Abstract

Dendritic cells form a system of highly efficient antigen-presenting cells. After capturing antigen in the periphery, they migrate to lymphoid organs where they present the antigen to T cells1,2. Their seemingly unique ability to interact with and sensitize naive T cells gives dendritic cells a central role in the initiation of immune responses and allows them to be used in therapeutic strategies against cancer, viral infection and other diseases. How they interact preferentially with naive rather than activated T lymphocytes is still poorly understood. Chemokines direct the transport of white blood cells in immune surveillance3,4. Here we report the identification and characterization of a C-C chemokine (DC-CK1) that is specifically expressed by human dendritic cells at high levels. Tissue distribution analysis demonstrates that dendritic cells present in germinal centres and T-cell areas of secondary lymphoid organs express this chemokine. We show that DC-CK1, in contrast to RANTES, MIP-1α and interleukin-8, preferentially attracts naive T cells (CD45RA+). The specific expression of DC-CK1 by dendritic cells at the site of initiation of an immune response, combined with its chemotactic activity for naive T cells, suggests that DC-CK1 has an important rule in the induction of immune responses.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: a, Nucleotide and amino-acid sequence of DC-CK1.
Figure 2: DC-CK1 mRNA is specifically expressed by dendritic cells.
Figure 3: Detection of DC-CK1 in germinal centres and T-cell areas of a tonsil by in situ hybridization.
Figure 4: DC-CK1 is a potent chemoattractant for the CD45RA+T-cell subset.

Similar content being viewed by others

References

  1. Steinman, R. M. The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9, 271–296 (1991).

    Article  CAS  Google Scholar 

  2. Marland, G., Bakker, A. B. H., Adema, G. J. & Figdor, C. G. Dendritic cells in immune response induction. Stem Cells 14, 501–507 (1997).

    Article  Google Scholar 

  3. Oppenheimer, J. J., Zachariae, C. O. C., Mukaida, N. & Matsushima, K. Properties of the novel proinflammatory supergene intercine cytokine family. Annu. Rev. Immunol. 9, 617–648 (1991).

    Article  Google Scholar 

  4. Schall, T. in The Cytokine Handbook (ed. Thompson, A.) 418–460 (Academic, New York, 1994).

    Google Scholar 

  5. Sallusto, F. & Lanzavecchia, A. 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).

    Article  CAS  Google Scholar 

  6. Romani, N.et al. Proliferating dendritic cell progenitors in human blood. J. Exp. Med. 180, 83–93 (1994).

    Article  CAS  Google Scholar 

  7. Bakker, A. B. H.et al. Generation of anti-melanoma CTL from healthy donors after presentation of melanoma associated antigen derived epitopes by dendritic cells in vitro. Cancer Res. 55, 5330–5334 (1995).

    CAS  PubMed  Google Scholar 

  8. Baumhueter, S.et al. Binding of L-selectin to the Vascular sialomucin CD34. Science 262, 436–438 (1993).

    Article  ADS  CAS  Google Scholar 

  9. Grouard, G., Durand, I., Filgueira, L., Banchereau, J. & Liu, Y.-J. Dendritic cells capable of stimulating T cells in germinal centers. Nature 384, 364–367 (1996).

    Article  ADS  CAS  Google Scholar 

  10. Schall, T. J., Bacon, K., Toy, K. J. & Goeddel, D. V. Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 347, 669–672 (1991).

    Article  ADS  Google Scholar 

  11. Schall, T. J., Bacon, K., Camp, R. D. R., Kaspari, J. W. & Goeddel, D. V. Human Mip-1α and Mip-1B chemokines attract distinct Populations of lymphocytes. J. Exp. Med. 177, 1821–1825 (1993).

    Article  CAS  Google Scholar 

  12. Ross, J. S., Mistry, K., Bacon, K. B. & Camp, R. D. Characterisation of the in vitro responsiveness of lymphocyte subsets to locomotor stimuli by immunocytochemical methods. J. Immunol. Meth. 140, 219–225 (1991).

    Article  CAS  Google Scholar 

  13. Katz, A., Wu, D. & Simon, M. I. Subunits βγ of heterotrimeric G protein activate γ2 isoform of phospholipase C. Nature 360, 686–689 (1992).

    Article  ADS  CAS  Google Scholar 

  14. Peters, J. H., Gieseler, R., Thiele, B. & Steinbach, F. Dendritic cells: from ontogenic orphans to myelomonocytic descendants. Immunol. Today 17, 273–278 (1996).

    Article  CAS  Google Scholar 

  15. Cocchi, F.et al. Identification of RANTES, Mip-1α and Mip-1β as the major HIV-suppressive factors produced by CD8+ T cells. Science 270, 1811–1815 (1995).

    Article  ADS  CAS  Google Scholar 

  16. Premack, B. A. & Schall, T. J. Chemokine receptors: Gateways to inflammation and infection. Nature Med. 11, 1174–1178 (1996).

    Article  Google Scholar 

  17. Figdor, C. G., Bont, W. S., Touw, I., Roosnek, E. E. & de Vries, J. E. Isolation of functionally different human monocytes by counterflow centrifugation elutriation. Blood 60, 46–53 (1982).

    CAS  PubMed  Google Scholar 

  18. Groningen, vanJ. J., Bloemers, H. P. & Swart, G. W. Identification of melanoma inhibitory activity and human melanoma cell lines with different metastatic capacity by messenger RNA differential display. Cancer Res. 15, 6237–6243 (1995).

    Google Scholar 

  19. Bacon, K. B., Camp, R. D., Cunningham, F. M. & Woollard, P. M. Contrating in vitro lymphocyte chemotactic activity of the hydroxyl enantiomers of 12-hydroxy-5,8,10,14-eicosatetraenoic acid. Br. J. Pharmacol. 95, 966–972 (1988).

    Article  CAS  Google Scholar 

  20. Mattijssen, V.et al. Clinical and immunopathological results of a phase II study of perilymphatically injected recombinant IL-2 in locally far advanced head and neck squamous cell carcinoma. J. Immunother. 10, 63–68 (1991).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank S. Zurawski, D. Gorman, F. Vega, R. Kastelein, M. Bell, K. Franz-Bacon, D.Figueroa, M. Koningswieser, R. Huijbens, C. Maass and L. Schalkwijk for assistance, and G. Zurawski, D. Ruiter and P. de Mulder for support. The DNAX Research Institute is supported by Schering Ploung Corporation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gosse J. Adema.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adema, G., Hartgers, F., Verstraten, R. et al. A dendritic-cell-derived C–C chemokine that preferentially attracts naive T cells. Nature 387, 713–717 (1997). https://doi.org/10.1038/42716

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/42716

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing