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

TY - JOUR

T1 - Development of interleukin-17-producing Vγ2+ γδ T cells is reduced by ICOS signaling in the thymus

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.

KW - Development

KW - ICOS

KW - Immune response

KW - Immunity

KW - Immunology and Microbiology Section

KW - Interleukin-17

KW - Thymus

KW - γδ T cell

U2 - 10.18632/oncotarget.8464

DO - 10.18632/oncotarget.8464

M3 - Journal article

C2 - 27235509

AN - SCOPUS:84964747492

SN - 1949-2553

VL - 7

SP - 19341

EP - 19354

JO - OncoTarget

JF - OncoTarget

IS - 15

ER -