Glutamate released by dendritic cells as a novel modulator of T cell activation

Rodrigo Pacheco, Harold Oliva, José M. Martinez-Navío, Núria Climent, Francisco Ciruela, José M. Gatell, Teresa Gallart, Josefa Mallol, Carmen Lluis, Rafael Franco

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Adaptive immune responses begin after productive immunosynaptic contacts formation established in secondary lymphoid organs by dendritic cells (DC) presenting the Ag to T lymphocytes. Despite its resemblance to the neurosynapse, the participation of soluble small nonpeptidic mediators in the intercellular cross-talk taking place during T cell-DC interactions remains poorly studied. In this study, we show that human DC undergoing maturation and in contact with T cells release significant amounts of glutamate, which is the main excitatory neurotransmitter in mammalians. The release of glutamate is nonvesicular and mediated by the DC-expressed Xc- cystine/glutamate antiporter. DC-derived glutamate stimulating the constitutively expressed metabotropic glutamate receptor 5 impairs T cell activation. However, after productive Ag presentation, metabotropic glutamate receptor 1 is expressed in T cells to mediate enhanced T cell proliferation and secretion of Th1 and proinflammatory cytokines. These data suggest that, during T cell-DC interaction, glutamate is a novel and highly effective regulator in the initiation of T cell-mediated immune responses.

Original languageEnglish (US)
Pages (from-to)6695-6704
Number of pages10
JournalJournal of Immunology
Volume177
Issue number10
DOIs
StatePublished - Nov 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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