title: Differentiation, phenotype, and function of interleukin-17-producing human Vγ9Vδ2 T cells.
abstract: In healthy adults, the major peripheral blood γδ T-cell subset expresses the Vγ9Vδ2 TCR and displays pleiotropic features. Here we report that coculture of naive Vγ9Vδ2 T cells with phosphoantigens and a cocktail of cytokines (IL-1-β, TGF-β, IL-6, and IL-23), leads to selective expression of the transcription factor RORγt and polarization toward IL-17 production. IL-17(+) Vγ9Vδ2 T cells express the chemokine receptor CCR6 and produce IL-17 but neither IL-22 nor IFN-γ; they have a predominant terminally differentiated (CD27(-)CD45RA(+)) phenotype and express granzyme B, TRAIL, FasL, and CD161. On antigen activation, IL-17(+) Vγ9Vδ2 T cells rapidly induce CXCL8-mediated migration and phagocytosis of neutrophils and IL-17-dependent production of β-defensin by epithelial cells, indicating that they may be involved in host immune responses against infectious microorganisms. Accordingly, an increased percentage of IL-17(+) Vγ9Vδ2 lymphocytes is detected in the peripheral blood and at the site of disease in children with bacterial meningitis, and this pattern was reversed after successful antibacterial therapy. Most notably, the phenotype of IL-17(+) Vγ9Vδ2 T cells in children with meningitis matches that of in vitro differentiated IL-17(+) Vγ9Vδ2 T cells. Our findings delineate a previously unknown subset of human IL-17(+) Vγ9Vδ2 T lymphocytes implicated in the pathophysiology of inflammatory responses during bacterial infections.
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Caccamo
authors.forename: Carmela
authors.initials: C
authors.lastname: La Mendola
authors.forename: Valentina
authors.initials: V
authors.lastname: Orlando
authors.forename: Serena
authors.initials: S
authors.lastname: Meraviglia
authors.forename: Matilde
authors.initials: M
authors.lastname: Todaro
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stassi
authors.forename: Guido
authors.initials: G
authors.lastname: Sireci
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008297:Male; D016920:Meningitis, Bacterial / Q000276:immunology* / Q000503:physiopathology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D023083:beta-Defensins / Q000276:immunology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; C508606:CXCL8 protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D016692:Receptors, Antigen, T-Cell, gamma-delta; D023083:beta-Defensins