Development of interleukin-17-producing Vγ2+ γδ T cells is reduced by ICOS signaling in the thymus

Terkild Brink Buus; Jonas Damgård Schmidt; Charlotte Menné Bonefeld; Carsten Geisler; Jens Peter Holst Lauritsen

doi:10.18632/oncotarget.8464

Development of interleukin-17-producing Vγ2⁺ γδ T cells is reduced by ICOS signaling in the thymus

Terkild Brink Buus^*, Jonas Damgård Schmidt, Charlotte Menné Bonefeld, Carsten Geisler, Jens Peter Holst Lauritsen

^*Corresponding author for this work

8 Citations (Scopus)

353 Downloads (Pure)

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⁺CD45RB^low 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.

Original language	English
Journal	OncoTarget
Volume	7
Issue number	15
Pages (from-to)	19341-19354
Number of pages	14
ISSN	1949-2553
DOIs	https://doi.org/10.18632/oncotarget.8464
Publication status	Published - 29 Mar 2016

Keywords

Development
ICOS
Immune response
Immunity
Immunology and Microbiology Section
Interleukin-17
Thymus
γδ T cell

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Development of interleukin-17-producing Vγ2+ γδ T cells is reduced by ICOS signaling in the thymusFinal published version, 5.45 MBLicence: CC BY

Cite this

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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.",

keywords = "Development, ICOS, Immune response, Immunity, Immunology and Microbiology Section, Interleukin-17, Thymus, γδ T cell",

author = "Buus, {Terkild Brink} and Schmidt, {Jonas Damg{\aa}rd} and Bonefeld, {Charlotte Menn{\'e}} and Carsten Geisler and Lauritsen, {Jens Peter Holst}",

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AU - Buus, Terkild Brink

AU - Schmidt, Jonas Damgård

AU - Bonefeld, Charlotte Menné

AU - Geisler, Carsten

AU - Lauritsen, Jens Peter Holst

PY - 2016/3/29

Y1 - 2016/3/29

N2 - 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.

AB - 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.

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KW - Immune response

KW - Immunity

KW - Immunology and Microbiology Section

KW - Interleukin-17

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KW - γδ T cell

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