A Synaptic Basis for Paracrine Interleukin-2 Signaling during Homotypic T Cell Interaction

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Abstract

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. © 2008 Elsevier Inc. All rights reserved.

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Sabatos, C. A., Doh, J., Chakravarti, S., Friedman, R. S., Pandurangi, P. G., Tooley, A. J., & Krummel, M. F. (2008). A Synaptic Basis for Paracrine Interleukin-2 Signaling during Homotypic T Cell Interaction. Immunity, 29(2), 238–248. https://doi.org/10.1016/j.immuni.2008.05.017

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