Adenosine triphosphate acts as a paracrine signaling molecule to reduce the motility of T cells

Organization of immune responses requires exchange of information between cells. This is achieved through either direct cell-cell contacts and establishment of temporary synapses or the release of soluble factors, such as cytokines and chemokines. Here we show a novel form of cell-to-cell communication based on adenosine triphosphate (ATP). ATP released by stimulated T cells induces P2X4/P2X7-mediated calcium waves in the neighboring lymphocytes. Our data obtained in lymph node slices suggest that, during T-cell priming, ATP acts as a paracrine messenger to reduce the motility of lymphocytes and that this may be relevant to allow optimal tissue scanning by T cells. Synopsis In reactive lymph nodes, ATP released by stimulated T cells is a paracrine signal to alarm the neighboring lymphocytes and reduce their motility. ATP released by stimulated T cells induces calcium waves in non-adhering, bystander T cells. P2X4 and P2X7 receptors are both involved in paracrine ATP signaling among lymphocytes. ATP signaling inhibits bystander cell motility during T-cell activation in lymph nodes. ATP released by activated T cells induces P2X4/P2X7-mediated calcium waves in neighboring lymphocytes leading to reduced lymphocytes motility that promotes more effective antigen scanning.