CXCR4–CCR5: a couple modulating T cell functions

RL Contento, B Molon, C Boularan… - Proceedings of the …, 2008 - National Acad Sciences
RL Contento, B Molon, C Boularan, T Pozzan, S Manes, S Marullo, A Viola
Proceedings of the National Academy of Sciences, 2008National Acad Sciences
Chemokines and their receptors direct leukocyte migration among blood, lymph and tissues.
Evidence has recently accumulated that, besides their chemotactic functions, chemokine
receptors are highly versatile players that fine tune immune responses. During human T cell
activation by antigen-presenting cells, the chemokine receptors CCR5 and CXCR4 are
recruited into the immunological synapse, where they deliver costimulatory signals.
However, the molecular mechanisms allowing signaling versatility of chemokine receptors …
Chemokines and their receptors direct leukocyte migration among blood, lymph and tissues. Evidence has recently accumulated that, besides their chemotactic functions, chemokine receptors are highly versatile players that fine tune immune responses. During human T cell activation by antigen-presenting cells, the chemokine receptors CCR5 and CXCR4 are recruited into the immunological synapse, where they deliver costimulatory signals. However, the molecular mechanisms allowing signaling versatility of chemokine receptors are unknown. Here, we describe the functional interaction between CXCR4 and CCR5 to exert specific biological functions and modulate T lymphocyte responses. We demonstrate that simultaneous expression and cooperation between CCR5 and CXCR4 are required for chemokine-induced T cell costimulation at the immunological synapse. In addition, we provide evidence for a physical association of the two receptors in a signaling complex that activates distinct T cell functions. We suggest that cooperation between receptors represents one key strategy for the functional plasticity of chemokines.
National Acad Sciences