Synaptic release of CCL5 storage vesicles triggers CXCR4 surface expression promoting CTL Migration in response to CXCL12

Katarzyna Franciszkiewicz, Marie Boutet, Ludiane Gauthier, Isabelle Vergnon, Kelly Peeters, Olivier Duc, Benjamin Besse, Geneviève De Saint Basile, Salem Chouaib, Fathia Mami-Chouaib

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The lytic function of CTL relies on the polarized release of cytotoxic granules (CG) at the immune synapse (IS) with target cells. CTL also contain CCL5 in cytoplasmic storage vesicles (CCL5V) distinct from CG, the role of which, in regulating T cell effector functions, is not understood. Using human CD8+ T cells specific to a lung tumor-associated Ag, we show in this article that CTL release both secretory compartments into the immune synapse with autologous tumor cells. Moreover, we demonstrate that disorganization of the T cell microtubule cytoskeleton and defects in hMunc13-4 or Rab27a abrogate CG exocytosis and synaptic secretion of the chemokine. Mechanistically, synaptic release of CCL5 cytoplasmic storage vesicles likely occurs upon their coalescence with the Rab27a-hMunc13-4 compartment and results in autocrine, CCR5-dependent induction of CXCR4 cell surface expression, thereby promoting T cell migration in response to CXCL12.We propose that CCL5 polarized delivery represents a mechanism by which CTL control immune synapse duration.

Original languageEnglish (US)
Pages (from-to)4952-4961
Number of pages10
JournalJournal of Immunology
Volume193
Issue number10
DOIs
StatePublished - Nov 15 2014
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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