title: Development of interleukin-17-producing Vγ2+ γδ T cells is reduced by ICOS signaling in the thymus.
abstract: Co-stimulation is an integral part of T cell signaling involved in almost all facets of T cell biology. While much is known about co-stimulation in differentiation and function of conventional αβ T cells, less is known about how co-stimulation affects the development and programming of γδ T cells. In this study, we have investigated the role of inducible T cell co-stimulator (ICOS) on the development of γδ T cells. We show that ICOS is expressed by a population of immature Vγ2+CD45RBlow γδ T cells predisposed to interleukin-17 (IL-17) production. We found that treatment with ICOS specific antibodies drastically reduces fetal development of IL-17-producing γδ T cells by agonistic actions, and that ICOS deficient mice have a significant increase in the population of IL-17-producing Vγ2+ γδ T cells in the thymus, spleen, lymph nodes and skin and exhibit exacerbated sensitization responses to 2,4-dinitrofluorobenzene. In conclusion, this study demonstrates that development of IL-17-producing Vγ2+ γδ T cells is reduced by ICOS signaling in the thymus.
authors.affiliation: Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Terkild Brink
authors.initials: TB
authors.lastname: Buus
authors.affiliation: Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jonas Damgård
authors.initials: JD
authors.lastname: Schmidt
authors.affiliation: Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Charlotte Menné
authors.initials: CM
authors.lastname: Bonefeld
authors.affiliation: Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.affiliation: Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens Peter Holst
authors.initials: JP
authors.lastname: Lauritsen
mesh_terms: D000818:Animals; D004139:Dinitrofluorobenzene / Q000276:immunology / Q000494:pharmacology; D005434:Flow Cytometry; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology* / Q000378:metabolism
chemical_list: C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D004139:Dinitrofluorobenzene
keywords: ICOS; Immune response; Immunity; Immunology and Microbiology Section; development; interleukin-17; thymus; γδ T cell