Don't Distract Me

Abstract

T cells receive both activating "stop" signals through ligation of the T cell receptor (TCR) and chemotactic or chemokinetic "go" signals from secreted chemokines. Molon et al . suggest that soluble chemokines released by the antigen-presenting cell (APC) may also contribute to the "stop" signal that stabilizes the immunological synapse formed between the T cell and the APC. Using green fluorescent protein (GFP)-tagged CCR5, a G protein-coupled chemokine receptor, they observed that CCR5 accumulated at the immunological synapse through a mechanism that did not require G i (it was not inhibited by pertussis toxin) but instead may involve coupling to G q or G 11 . This recruitment of CCR5 was inhibited if the cells were exposed to a CCR5 antagonist or if the APCs were treated with monensin, a nonspecific inhibitor of protein secretion. Furthermore, T cells that were prebound to APCs that were exposed to antigen and that had not been treated with monensin (conditions in which the CCR5 was incorporated into the immunological synapse) were less responsive to a chemotactic signal than were T cells that were either prebound to APCs that had not been exposed to antigen or antigen-exposed APCs that had been treated with monensin. In addition, stimulation of T cells with beads coated with either an antibody against CD3 (a protein in the TCR complex) or anti-CD3 plus CCR5 and CXCR4 agonists resulted in strong stimulation of T cell proliferation and interferon γ secretion comparable to that observed for T cells stimulated with antigen and a costimulatory signal. The authors propose that recruitment of selective chemokine receptors to the immunological synapse may serve to sequester these receptors, thus making the T cells less "distracted" by chemotactic signals. This may further serve as a costimulatory signal. In commentary on this article, Trautmann suggests that chemokines may be "immunotransmitters" analogous to the neurotransmitters released at neuronal synapses. B. Molon, G. Gri, M. Bettella, C. Gómez-Moutón, A. Lanzavecchia, C. Martínez-A, S. Mañes, A. Viola, T cell costimulation by chemokine receptors. Nat. Immunol. 6 , 465-471 (2005). [PubMed] A. Trautmann, Chemokines as immunotransmitters? Nat. Immunol. 6 , 427-428 (2005). [PubMed]