Glutamate released by dendritic cells as a novel modulator of T cell activation.
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.
Pacheco
Rodrigo
R
Department of Biochemistry and Molecular Biology, Faculty of Biology and Institut d'Investigació Biomèdica August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Oliva
Harold
H
Martinez-Navío
José M
JM
Climent
Núria
N
Ciruela
Francisco
F
Gatell
José M
JM
Gallart
Teresa
T
Mallol
Josefa
J
Lluis
Carmen
C
Franco
Rafael
R
D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D020239:Receptor Cross-Talk / Q000276:immunology; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid