T cell costimulation by chemokine receptors
Molon B, Gri G, Bettella M, Gomez-Mouton C, Lanzavecchia A, Martinez-A C, Manes S and Viola A
Immunotherapy / Hematology
Cells used in publication:
T cell, human peripheral blood unstim.
Tissue Origin: blood
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.
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