A synaptic basis for paracrine interleukin-2 signaling during homotypic T cell interaction

T cells slow their motility, increase adherence, and arrest after encounters with antigen-presenting cells (APCs) bearing peptide-MHC complexes. Here, we analyzed the cell-cell communication among activating T cells. In vivo and in vitro, activating T cells associated in large clusters that collectively persisted for > 30 min, but they also engaged in more transient interactions, apparently distal to APCs. Homotypic aggregation was driven by LFA-1 integrin interactions. Ultrastructural analysis revealed that cell-cell contacts between activating T cells were organized as multifocal synapses, and T cells oriented both the microtubule-organizing complex and interleukin-2 (IL-2) secretion toward this synapse. T cells engaged in homotypic interactions more effectively captured IL-2 relative to free cells. T cells receiving paracrine synaptic IL-2 polarized their IL-2 signaling subunits into the synaptic region and more efficiently phosphorylated the transcription factor STAT5, likely through a synapse-associated signaling complex. Thus, synapse-mediated cytokine delivery accelerates responses in activating T cells.