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T cell costimulation by chemokine receptors

Nature Immunology volume 6, pages 465–471 (2005)Cite this article

Abstract

Signals mediated by chemokine receptors may compete with T cell receptor stop signals and determine the duration of T cell–antigen-presenting cell interactions. Here we show that during T cell stimulation by antigen-presenting cells, T cell chemokine receptors coupled to Gq and/or G11 protein were recruited to the immunological synapse by a Gi-independent mechanism. When chemokine receptors were sequestered at the immunological synapse, T cells became insensitive to chemotactic gradients, formed more stable conjugates and finally responded with enhanced proliferation and cytokine production. We suggest that chemokine receptor trapping at the immunological synapse enhances T cell activation by improving T cell–antigen-presenting cell attraction and impeding the 'distraction' of successfully engaged T cells by other chemokine sources.

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Figure 1: CCR5 is recruited to the T cell IS.
Figure 2: CCR5 recruitment to the T cell–APC contact site requires the formation of a productive IS.
Figure 3: Recruitment of chemokine receptors to the IS depends on chemokines released by APCs.
Figure 4: CCR5 engaged at the IS is coupled to Gq and/or G11.
Figure 5: Chemokine receptor recruitment to the IS reduces T cell responsiveness to chemoattractants.
Figure 6: CCR7 is not recruited to the IS.
Figure 7: Chemokine receptors enhance T cell activation.

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Acknowledgements

We thank T. Pozzan for support. Supported by the Italian Ministry of Health (Ricerca finalizzata), US Army (DAMD17-03-1-0032), Italian Association for Cancer Research and University of Padua Progetto d'Ateneo (A.V.); and the Spanish Ministry of Science and Education and Fundación Lilly (C.M.). The Department of Immunology and Oncology was founded by and is supported by the Spanish Council for Scientific Research and by Pfizer.

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Authors and Affiliations

  1. Venetian Institute of Molecular Medicine and Department of Biomedical Science, University of Padua, Padua, 35100, Italy

    Barbara Molon, Giorgia Gri, Monica Bettella & Antonella Viola

  2. Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Madrid, 28049, Spain

    Concepción Gómez-Moutón, Carlos Martínez-A & Santos Mañes

  3. Institute for Research in Biomedicine, Bellinzona, 6500, Switzerland

    Antonio Lanzavecchia

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  1. Barbara Molon
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Supplementary information

Supplementary Fig. 1

CXCR4 recruitment to the T cell–APC contact site requires the formation of a productive IS and of CXCL12 released by APCs. (PDF 831 kb)

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Molon, B., Gri, G., Bettella, M. et al. T cell costimulation by chemokine receptors. Nat Immunol 6, 465–471 (2005). https://doi.org/10.1038/ni1191

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