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.

  • Overview
  • Published:

Chemokines and leukocyte traffic

Abstract

Twenty years after the discovery of chemokines is an appropriate time to review leukocyte traffic and to assess the knowledge and opportunities that have arisen from countless studies of the large and tight-knit family of chemotactic proteins.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

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

References

  1. Baggiolini, M. Chemokines and leukocyte traffic. Nature 392, 565–568 (1998).

    Article  CAS  Google Scholar 

  2. 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  CAS  Google Scholar 

  3. Loetscher, P., Seitz, M., Baggiolini, M. & Moser, B. Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes. J. Exp. Med. 184, 569–577 (1996).

    Article  CAS  Google Scholar 

  4. Sallusto, F., Mackay, C.R. & Lanzavecchia, A. Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science 277, 2005–2007 (1997).

    Article  CAS  Google Scholar 

  5. Sallusto, F., Lenig, D., Mackay, C.R. & Lanzavecchia, A. Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J. Exp. Med. 187, 875–883 (1998).

    Article  CAS  Google Scholar 

  6. Springer, T.A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76, 301–314 (1994).

    Article  CAS  Google Scholar 

  7. Butcher, E.C. & Picker, L.J. Lymphocyte homing and homeostasis. Science 272, 60–66 (1996).

    Article  CAS  Google Scholar 

  8. Matloubian, M. et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427, 355–360 (2004).

    Article  CAS  Google Scholar 

  9. Oppenheim, J.J. & Yang, D. Alarmins: chemotactic activators of immune responses. Curr. Opin. Immunol. 17, 359–365 (2005).

    Article  CAS  Google Scholar 

  10. Forster, R. et al. A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell 87, 1037–1047 (1996).

    Article  CAS  Google Scholar 

  11. Forster, R. et al. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99, 23–33 (1999).

    Article  CAS  Google Scholar 

  12. Gunn, M.D. et al. Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J. Exp. Med. 189, 451–460 (1999).

    Article  CAS  Google Scholar 

  13. Nagasawa, T. et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382, 635–638 (1996).

    Article  CAS  Google Scholar 

  14. Zou, Y.R., Kottmann, A.H., Kuroda, M., Taniuchi, I. & Littman, D.R. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393, 595–599 (1998).

    Article  CAS  Google Scholar 

  15. Sierro, F. et al. Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7. Proc. Natl. Acad. Sci. USA 104, 14759–14764 (2007).

    Article  CAS  Google Scholar 

  16. Wells, T.N., Power, C.A., Shaw, J.P. & Proudfoot, A.E. Chemokine blockers–therapeutics in the making? Trends Pharmacol. Sci. 27, 41–47 (2006).

    Article  CAS  Google Scholar 

  17. Miller, D.H. et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 348, 15–23 (2003).

    Article  CAS  Google Scholar 

  18. Germain, R.N., Miller, M.J., Dustin, M.L. & Nussenzweig, M.C. Dynamic imaging of the immune system: progress, pitfalls and promise. Nat. Rev. Immunol. 6, 497–507 (2006).

    Article  CAS  Google Scholar 

  19. Miller, M.J., Wei, S.H., Parker, I. & Cahalan, M.D. Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296, 1869–1873 (2002).

    Article  CAS  Google Scholar 

  20. Friedl, P. & Weigelin, B. Interstitial leukocyte migration and immune function. Nat Immunol. 9, 960–969 (2008).

    Article  CAS  Google Scholar 

  21. Mempel, T.R., Henrickson, S.E. & Von Andrian, U.H. T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427, 154–159 (2004).

    Article  CAS  Google Scholar 

  22. Lindquist, R.L. et al. Visualizing dendritic cell networks in vivo. Nat. Immunol. 5, 1243–1250 (2004).

    Article  CAS  Google Scholar 

  23. Hugues, S. et al. Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity. Nat. Immunol. 5, 1235–1242 (2004).

    Article  CAS  Google Scholar 

  24. Lanzavecchia, A., Lezzi, G. & Viola, A. From TCR engagement to T cell activation: a kinetic view of T cell behavior. Cell 96, 1–4 (1999).

    Article  CAS  Google Scholar 

  25. Friedl, P. & Gunzer, M. Interaction of T cells with APCs: the serial encounter model. Trends Immunol. 22, 187–191 (2001).

    Article  CAS  Google Scholar 

  26. Castellino, F. et al. Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature 440, 890–895 (2006).

    Article  CAS  Google Scholar 

  27. Allen, C.D., Okada, T., Tang, H.L. & Cyster, J.G. Imaging of germinal center selection events during affinity maturation. Science 315, 528–531 (2007).

    Article  CAS  Google Scholar 

  28. Kuschert, G.S. et al. Glycosaminoglycans interact selectively with chemokines and modulate receptor binding and cellular responses. Biochemistry 38, 12959–12968 (1999).

    Article  CAS  Google Scholar 

  29. Wolf, M., Albrecht, S. & Marki, C. Proteolytic processing of chemokines: implications in physiological and pathological conditions. Int. J. Biochem. Cell Biol. 40, 1185–1198 (2008).

    Article  CAS  Google Scholar 

  30. Paoletti, S. et al. A rich chemokine environment strongly enhances leukocyte migration and activities. Blood 105, 3405–3412 (2005).

    Article  CAS  Google Scholar 

  31. Bromley, S.K., Mempel, T.R. & Luster, A.D. Orchestrating the orchestrators: chemokines in control of T cell traffic. Nat Immunol. 9, 970–980 (2008).

    Article  CAS  Google Scholar 

  32. Sigmundsdottir, H. & Butcher, E.C. Environmental cues, dendritic cells and the programming of tissue-selective lymphocyte trafficking. Nat Immunol. 9, 981–987 (2008).

    Article  CAS  Google Scholar 

  33. Sallusto, F., Geginat, J. & Lanzavecchia, A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu. Rev. Immunol. 22, 745–763 (2004).

    Article  CAS  Google Scholar 

  34. Acosta-Rodriguez, E.V. et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat. Immunol. 8, 639–646 (2007).

    Article  CAS  Google Scholar 

  35. Guarda, G. et al. L-selectin-negative CCR7 effector and memory CD8+ T cells enter reactive lymph nodes and kill dendritic cells. Nat. Immunol. 8, 743–752 (2007).

    Article  CAS  Google Scholar 

  36. Martin-Fontecha, A. et al. Induced recruitment of NK cells to lymph nodes provides IFN-γ for TH1 priming. Nat. Immunol. 5, 1260–1265 (2004).

    Article  CAS  Google Scholar 

  37. Campbell, J.J. et al. The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature 400, 776–780 (1999).

    Article  CAS  Google Scholar 

  38. Schaerli, P. et al. A skin-selective homing mechanism for human immune surveillance T cells. J. Exp. Med. 199, 1265–1275 (2004).

    Article  CAS  Google Scholar 

  39. Blanpain, C. et al. The core domain of chemokines binds CCR5 extracellular domains while their amino terminus interacts with the transmembrane helix bundle. J. Biol. Chem. 278, 5179–5187 (2003).

    Article  CAS  Google Scholar 

  40. Loetscher, P. & Clark-Lewis, I. Agonistic and antagonistic activities of chemokines. J. Leukoc. Biol. 69, 881–884 (2001).

    CAS  PubMed  Google Scholar 

  41. Baggiolini, M., Dewald, B. & Moser, B. Human chemokines: an update. Annu. Rev. Immunol. 15, 675–705 (1997).

    Article  CAS  Google Scholar 

  42. Thelen, M. et al. Mechanism of neutrophil activation by NAF, a novel monocyte-derived peptide agonist. FASEB J. 2, 2702–2706 (1988).

    Article  CAS  Google Scholar 

  43. Thelen, M. & Stein, J.V. How chemokines invite leukocyte to dance. Nat Immunol. 9, 953–959 (2008).

    Article  CAS  Google Scholar 

  44. Mackay, C.R. Moving targets: cell migration as new anti-inflammatory therapies. Nat Immunol. 9, 988–998 (2008).

    Article  CAS  Google Scholar 

  45. Schwartz, T.W., Frimurer, T.M., Holst, B., Rosenkilde, M.M. & Elling, C.E. Molecular mechanism of 7TM receptor activation–a global toggle switch model. Annu. Rev. Pharmacol. Toxicol. 46, 481–519 (2006).

    Article  CAS  Google Scholar 

  46. Romagnani, P., Lasagni, L., Annunziato, F., Serio, M. & Romagnani, S. CXC chemokines: the regulatory link between inflammation and angiogenesis. Trends Immunol. 25, 201–209 (2004).

    Article  CAS  Google Scholar 

  47. Glass, W.G. et al. CCR5 deficiency increases risk of symptomatic West Nile virus infection. J. Exp. Med. 203, 35–40 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank M. Uguccioni and A. Lanzavecchia for discussions and input. The Institute for Research in Biomedicine is supported by the Helmut Horten Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Federica Sallusto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sallusto, F., Baggiolini, M. Chemokines and leukocyte traffic. Nat Immunol 9, 949–952 (2008). https://doi.org/10.1038/ni.f.214

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni.f.214

This article is cited by

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