title: Human Vδ2 T cells are a major source of interleukin-9.
abstract: Vδ2Vγ9 T cells are the dominant γδ T-cell subset in human peripheral blood. Vδ2 T cells recognize pyrophosphate molecules derived from microbes or tumor cells; hence, they play a role in antimicrobial and antitumor immunity. TGF-β, together with IL-15, induces a regulatory phenotype in Vδ2 T cells, characterized by forkhead box protein P3 (FoxP3) expression and suppressive activity on CD4 T-cell activation. We performed a genome-wide transcriptome analysis and found that the same conditions (TGF-β plus IL-15) strongly enhanced the expression of additional genes in Vδ2 T cells, including IKAROS family zinc finger 4 (IKZF4; Eos), integrin subunit alpha E (ITGAE; CD103/αEβ7), and IL9 This up-regulation was associated with potent IL-9 production as revealed by flow cytometry and multiplex analysis of cell culture supernatants. In contrast to CD4 and CD8 αβ T cells, γδ T cells did not require IL-4 for induction of intracellular IL-9 expression. Upon antigen restimulation of Vδ2 T cells expanded in vitro in the presence of TGF-β and IL-15, IL-9 was the most abundant among 16 analyzed cytokines and chemokines. IL-9 is a pleiotropic cytokine involved in various (patho)physiological conditions, including allergy and tumor defense, where it can promote antitumor immunity. Given the conspicuous sensitivity of many different tumors to Vδ2 T-cell-mediated killing, the conditions defined here for strong induction of IL-9 might be relevant for the development of Vδ2 T-cell-based immunotherapy.
authors: Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany.
authors: Christian
authors: 0000-0002-7669-3806
authors: C
authors: Peters
authors: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany.
authors: Robert
authors: R
authors: Häsler
authors: Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany.
authors: Daniela
authors: D
authors: Wesch
authors: Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, D-24105 Kiel, Germany; dietrich.kabelitz@uksh.de.
authors: Dieter
authors: D
authors: Kabelitz
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D049690:History, Ancient; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D019409:Interleukin-15; D016906:Interleukin-9; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016212:Transforming Growth Factor beta
keywords: human; interleukin-9; transforming growth factor-β; γ/δ T cells