title: Potentiation of antigen-stimulated V gamma 9V delta 2 T cell cytokine production by immature dendritic cells (DC) and reciprocal effect on DC maturation.
abstract: Vgamma9Vdelta2 T cells, a major gammadelta PBL subset in human adults, have been previously implicated in dendritic cell (DC) licensing, owing to their high frequency in peripheral tissues and their ability to produce inflammatory cytokines upon recognition of a broad array of conserved Ags. Although these observations implied efficient recognition of Ag-expressing immature DC (iDC) by Vgamma9Vdelta2 T cells, the role played by DC subsets in activation of these lymphocytes has not been carefully studied so far. We show that iDC, and to a lesser extent mature DC, potentiated Th1 and Th2 cytokine, but not cytolytic or proliferative responses, of established Vgamma9Vdelta2 T cell clones and ex vivo memory Vgamma9Vdelta2 PBL stimulated by synthetic agonists. The ability of iDC to potentiate Vgamma9Vdelta2 production of inflammatory cytokines required for their own maturation suggested that Vgamma9Vdelta2 T cells, despite their strong lytic activity, could promote efficient iDC licensing without killing at suboptimal Ag doses. Accordingly Vgamma9Vdelta2 cells induced accelerated maturation of Ag-expressing iDC but not "bystander" DC, even within mixed cell populations comprising both Ag-expressing and nonexpressing iDC. Furthermore Vgamma9Vdelta2 cells induced full differentiation into IL-12-producing cells of iDC infected by Vgamma9Vdelta2-stimulating mycobacteria that were otherwise unable to induce complete DC maturation. In conclusion the ability of iDC to selectively potentiate cytokine response of memory Vgamma9Vdelta2 T cells could underlie the adjuvant effect of these lymphocytes, and possibly other natural memory T cells, on conventional T cell responses.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 601, Nantes, France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Devilder
authors.forename: Sophie
authors.initials: S
authors.lastname: Maillet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bouyge-Moreau
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Donnadieu
authors.forename: Marc
authors.initials: M
authors.lastname: Bonneville
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scotet
mesh_terms: D000941:Antigens / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D011756:Diphosphates / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009163:Mycobacterium bovis / Q000276:immunology; D000077268:Pamidronate; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000941:Antigens; D000970:Antineoplastic Agents; D016207:Cytokines; D011756:Diphosphates; D004164:Diphosphonates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; C429553:bromohydrin pyrophosphate; D000077268:Pamidronate; D002118:Calcium