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.
Sabatos
Catherine A
CA
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143-0511, USA.
Doh
Junsang
J
Chakravarti
Sumone
S
Friedman
Rachel S
RS
Pandurangi
Priya G
PG
Tooley
Aaron J
AJ
Krummel
Matthew F
MF
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019899:Paracrine Communication; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D050799:STAT5 Transcription Factor