Journal
ONCOTARGET
Volume 7, Issue 15, Pages 19341-19354Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8464
Keywords
gamma delta T cell; development; thymus; ICOS; interleukin-17; Immunology and Microbiology Section; Immune response; Immunity
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Funding
- Novo Nordisk Foundation
- Novo Nordisk Fonden [NNF10OC1013296] Funding Source: researchfish
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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 alpha beta T cells, less is known about how co-stimulation affects the development and programming of gamma delta T cells. In this study, we have investigated the role of inducible T cell co-stimulator (ICOS) on the development of gamma delta T cells. We show that ICOS is expressed by a population of immature V gamma 2(+)CD45RB(low) gamma delta 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 gamma delta T cells by agonistic actions, and that ICOS deficient mice have a significant increase in the population of IL-17-producing V gamma 2(+) gamma delta 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 V gamma 2(+) gamma delta T cells is reduced by ICOS signaling in the thymus.
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