T cell costimulation by chemokine receptors

Nat Immunol. 2005 May;6(5):465-71. doi: 10.1038/ni1191. Epub 2005 Apr 10.

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 G(q) and/or G(11) protein were recruited to the immunological synapse by a G(i)-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Cell Adhesion
  • Cells, Cultured
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Humans
  • Lymphocyte Activation / immunology*
  • Protein Binding
  • Receptors, Chemokine / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • Receptors, Chemokine
  • GTP-Binding Protein alpha Subunits, Gq-G11