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.

  • Article
  • Published:

A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo

Nature Immunology volume 1, pages 298–304 (2000)Cite this article

Abstract

We describe a protein with the hallmarks of a chemokine, designated CXCL16, that is made by dendritic cells (DCs) in lymphoid organ T cell zones and by cells in the splenic red pulp. CXCL16 contains a transmembrane domain and both membrane-bound and soluble forms are produced. Naïve CD8 T cells, natural killer T cells and a subset of memory CD4 T cells bind CXCL16, and activated T cells migrated chemotactically to the soluble chemokine. By expression cloning, Bonzo (also known as STRL33 and TYMSTR) was identified as a CXCL16 receptor. CXCL16 may function in promoting interactions between DCs and CD8 T cells and in guiding T cell movements in the splenic red pulp. CXCL16 was also found in the thymic medulla and in some nonlymphoid tissues, indicating roles in thymocyte development and effector T cell trafficking.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Amino acid sequence and alignment of mouse and human CXCL16.
Figure 2: Northern and western blot analyses of murine CXCL16.
Figure 3: Cell surface expression of CXCL16 on DCs.
Figure 4: Expression of CXCL16 in spleen, lymph node and thymus.
Figure 5: Expression of CXCL16 receptor by naïve and activated T cells.
Figure 6: Migration of activated T cells to CXCL16.
Figure 7: CXCR6 (Bonzo) is a functional receptor for CXCL16.

Similar content being viewed by others

References

  1. Oppenheim, J. J., Zachariae, C. O. C., Mukaida, J. & Matsushima, K. Properties of the novel proinflammatory supergene “intercrine” cytokine family. Annu. Rev. Immunol. 9, 617–648 (1991).

    Article  CAS  Google Scholar 

  2. Cyster, J. G. Chemokines and cell migration in secondary lymphoid organs. Science 286, 2098–2102 (1999).

    CAS  Google Scholar 

  3. Zlotnik, A., Morales, J. & Hedrick, J. A. Recent advances in chemokines and chemokine receptors. Crit. Rev. Immunol. 19, 1–47 (1999).

    Article  CAS  Google Scholar 

  4. Zlotnik, A. & Yoshie, O. Chemokines: a new classification system and their role in immunity. Immunity 12, 121–127 (2000).

    Article  CAS  Google Scholar 

  5. Pan, Y. et al. Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation Nature 387, 611–617 (1997). (Erratum: Nature 389, 100 (1997).)

    Article  CAS  Google Scholar 

  6. Bazan, J. F. et al. A new class of membrane-bound chemokine with a CX3C motif. Nature 385, 640–644 (1997).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Unutmaz, D., KewalRamani, V. N. & Littman, D. R. G. protein-coupled receptors in HIV and SIV entry: new perspectives on lentivirus-host interactions and on the utility of animal models. Semin. Immunol. 10, 225–236 (1998).

    Google Scholar 

  9. Pellas, T. C. & Weiss, L. Migration pathways of recirculating murine B cells and CD4+ and CD8+ T lymphocytes. Am. J. Anat. 187, 355–373 (1990).

    Article  CAS  Google Scholar 

  10. Willfuhr, K. U. & Westermann, J. Absolute numbers of lymphocyte subsets migrating through the compartments of the normal and transplanted rat spleen. Eur. J. Immunol. 20, 903–911 (1990).

    Article  CAS  Google Scholar 

  11. Potsch, C., Vohringer, D. & Pircher, H. Distinct migration patterns of naive and effector CD8 T cells in the spleen: correlation with CCR7 receptor expression and chemokine reactivity. Eur. J. Immunol. 29, 3562–3570 (1999).

    Article  CAS  Google Scholar 

  12. Trinchieri, G. Biology of natural killer cells. Adv. Immunol. 47, 187–376 (1989).

    Article  CAS  Google Scholar 

  13. Smith, K. G. C., Hewitson, T. D., Nossal, G. J. V. & Tarlinton, D. M. The phenotype and fate of the antibody-forming cells of the splenic foci. Eur. J. Immunol. 26, 444–448 (1996).

    Article  CAS  Google Scholar 

  14. Liao, F. et al. STRL33, a novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1. J. Exp. Med. 185, 2015–2023 (1997).

    Article  CAS  Google Scholar 

  15. Deng, H. K., Unutmaz, D., KewalRamani, V. N. & Littman, D. R. Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature 388, 296–300 (1997).

    Article  CAS  Google Scholar 

  16. Loetscher, M. et al. TYMSTR, a putative chemokine receptor selectively expressed in activated T cells, exhibits HIV-1 coreceptor function. Curr. Biol. 7, 652–660 (1997).

    Article  CAS  Google Scholar 

  17. Hofmann, K., Bucher, P., Falquet, L. & Bairoch, A. The PROSITE database, its status in 1999. Nucleic Acids Res. 27, 215–219 (1999).

    Article  CAS  Google Scholar 

  18. Cyster, J. G., Shotton, D. M. & Williams, A. F. The dimensions of the T lymphocyte glycoprotein leukosialin and identification of linear protein epitopes that can be modified by glycosylation. EMBO J. 10, 893–902 (1991).

    Article  CAS  Google Scholar 

  19. Abdullah, K. M., Udoh, E. A., Shewen, P. E. & Mellors, A. A neutral glycoprotease of Pasteurella haemolytica A1 specifically cleaves O-sialoglycoproteins. Infect. Immun. 60, 56–62 (1992).

    CAS  Google Scholar 

  20. Hooper, N. M., Karran, E. H. & Turner, A. J. Membrane protein secretases. Biochem. J. 321, 265–279 (1997).

    Article  CAS  Google Scholar 

  21. Edinger, A. L. et al. Use of GPR1, GPR15, and STRL33 as coreceptors by diverse human immunodeficiency virus type 1 and simian immunodeficiency virus envelope proteins. Virology 249, 367–378 (1998).

    Article  CAS  Google Scholar 

  22. Ngo, V. N., Tang, H. L. & Cyster, J. G. Epstein-Barr virus-induced molecule 1 ligand chemokine is expressed by dendritic cells in lymphoid tissues and strongly attracts naive T cells and activated B cells. J. Exp. Med. 188, 181–191 (1998).

    Article  CAS  Google Scholar 

  23. Sallusto, F. et al. Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur. J. Immunol. 29, 1617–1625 (1999).

    Article  CAS  Google Scholar 

  24. Tang, H. L. & Cyster, J. G. Chemokine upregulation and activated T cell attraction by maturing dendritic cells. Science 284, 819–822 (1999).

    Article  CAS  Google Scholar 

  25. Papadopoulos, E. J. et al. Fractalkine, a CX3C chemokine, is expressed by dendritic cells and is up-regulated upon dendritic cell maturation. Eur. J. Immunol. 29, 2551–2559 (1999).

    Article  CAS  Google Scholar 

  26. Kanazawa, N. et al. Fractalkine and macrophage-derived chemokine: T cell-attracting chemokines expressed in T cell area dendritic cells. Eur. J. Immunol. 29, 1925–1932 (1999).

    Article  CAS  Google Scholar 

  27. Lanzavecchia, A. License to kill. Nature 393, 413–414 (1998).

    Article  CAS  Google Scholar 

  28. Ridge, J. P., Di Rosa, F. & Matzinger, P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393, 474–478 (1998).

    Article  CAS  Google Scholar 

  29. Haanen, J. B. et al. Systemic T cell expansion during localized viral infection. Eur. J. Immunol. 29, 1168–1174 (1999).

    Article  CAS  Google Scholar 

  30. Ohmori, Y. et al. Tumor necrosis factor-alpha induces cell type and tissue-specific expression of chemoattractant cytokines in vivo. Am. J. Pathol. 142, 861–870 (1993).

    CAS  Google Scholar 

  31. Amichay, D. et al. Genes for chemokines MuMig and Crg-2 are induced in protozoan and viral infections in response to IFN-γ with patterns of tissue expression that suggest nonredundant roles in vivo. J. Immunol. 157, 4511–4520 (1996).

    CAS  Google Scholar 

  32. Bordessoule, D., Gaulard, P. & Mason, D. Y. Preferential localisation of human lymphocytes bearing γδ T cell receptors to the red pulp of the spleen. J. Clin. Pathol. 43, 461–464 (1990).

    Article  CAS  Google Scholar 

  33. Balazs, M., Grama, L. & Balogh, P. Detection of phenotypic heterogeneity within the murine splenic vasculature using rat monoclonal antibodies IBL-7/1 and IBL-7/22. Hybridoma 18, 177–182 (1999).

    Article  CAS  Google Scholar 

  34. Muehlhoefer, A. et al. Fractalkine is an epithelial and endothelial cell-derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa. J. Immunol. 164, 3368–3376 (2000).

    Article  CAS  Google Scholar 

  35. Bendelac, A., Rivera, M. N., Park, S. H. & Roark, J. H. Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu. Rev. Immunol. 15, 535–562 (1997).

    Article  CAS  Google Scholar 

  36. Alkhatib, G., Liao, F., Berger, E. A., Farber, J. M. & Peden, K. W. A new SIV co-receptor, STRL33 (letter; see comments). Nature 388, 238 (1997).

    Article  CAS  Google Scholar 

  37. Pohlmann, S., Krumbiegel, M. & Kirchhoff, F. Coreceptor usage of BOB/GPR15 and Bonzo/STRL33 by primary isolates of human immunodeficiency virus type 1. J. Gen. Virol. 80, 1241–1251 (1999).

    Article  CAS  Google Scholar 

  38. Zhang, Y. J. & Moore, J. P. Will multiple coreceptors need to be targeted by inhibitors of human immunodeficiency virus type 1 entry? J. Virol. 73, 3443–3448 (1999).

    CAS  Google Scholar 

  39. Van Vactor, D. V. & Lorenz, L. J. Neural development: the semantics of axon guidance. Curr. Biol. 9, R201–204 (1999).

    Article  CAS  Google Scholar 

  40. Holder, N. & Klein, R. Eph receptors and ephrins: effectors of morphogenesis. Development 126, 2033–2044 (1999).

    CAS  Google Scholar 

  41. Reif, K., Nobes, C. D., Thomas, G., Hall, A. & Cantrell, D. A. Phosphatidylinositol 3-kinase signals activate a selective subset of Rac/Rho-dependent effector pathways. Curr. Biol. 6, 1445–1455 (1996).

    Article  CAS  Google Scholar 

  42. Lane, P. et al. Activated human T cells express a ligand for the human B cell-associated antigen CD40 which participates in T cell-dependent activation of B lymphocytes. Eur. J. Immunol. 22, 2573–2578 (1992).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank P. Hyman for technical help, P. Lane for the Fc expression plasmid, C. Turck for protein sequencing, A. Weiss for helpful input and L. Mintz for comments on the manuscript. Supported by NIH grant AI45073 and Packard Foundation (to J. G. C.) and UCSF Molecular Medicine Training Program and NIH Academic Rheumatology and Clinical Immunology training grant AR07304 (to M. M.).

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, University of California San Francisco, San Francisco, 94143, CA, USA

    Mehrdad Matloubian & Jason G. Cyster

  2. Compugen Ltd., Tel-Aviv, Israel, 69512

    Anat David & Sharon Engel

  3. Department of Immunology and Medicine, VA Medical Center, San Francisco, 94121, CA, USA

    Jay E. Ryan

Authors
  1. Mehrdad Matloubian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anat David
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharon Engel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jay E. Ryan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jason G. Cyster
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jason G. Cyster.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matloubian, M., David, A., Engel, S. et al. A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol 1, 298–304 (2000). https://doi.org/10.1038/79738

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/79738

This article is cited by

Search

Advanced 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