Cited by 116T-cell and B-cell ImmunologyImmune Cell Function and InteractionPsoriasis: Treatment and Pathogenesis

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Five Layers of Receptor Signaling in Î³Î´ T-Cell Differentiation and Activation

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Ribeiro, SÃ©rgio T., Ribot, Julie C., Silva-Santos, Bruno·2015·Frontiers in Immunology

DOI 10.3389/fimmu.2015.00015PMC PMC4306313

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Abstract

The contributions of γδ T-cells to immunity to infection or tumors critically depend on their activation and differentiation into effectors capable of secreting cytokines and killing infected or transformed cells. These processes are molecularly controlled by surface receptors that capture key extracellular cues and convey downstream intracellular signals that regulate γδ T-cell physiology. The understanding of how environmental signals are integrated by γδ T-cells is critical for their manipulation in clinical settings. Here, we discuss how different classes of surface receptors impact on human and murine γδ T-cell differentiation, activation, and expansion. In particular, we review the role of five receptor types: the T-cell receptor (TCR), costimulatory receptors, cytokine receptors, NK receptors, and inhibitory receptors. Some of the key players are the costimulatory receptors CD27 and CD28, which differentially impact on pro-inflammatory subsets of γδ T-cells; the cytokine receptors IL-2R, IL-7R, and IL-15R, which drive functional differentiation and expansion of γδ T-cells; the NK receptor NKG2D and its contribution to γδ T-cell cytotoxicity; and the inhibitory receptors PD-1 and BTLA that control γδ T-cell homeostasis. We discuss these and other receptors in the context of a five-step model of receptor signaling in γδ T-cell differentiation and activation, and discuss its implications for the manipulation of γδ T-cells in immunotherapy.

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Authors: Ribeiro, S. T., Ribot, J. C., & Silva-Santos, B.
Affiliations: University of Lisbon (PT)
ORCID: Ribot, Julie C.
Venue: Frontiers in Immunology
Publisher: Frontiers Media SA
Published: 2015-01-26
Volume: 6
Pages: 15-15
ISSN: 1664-3224 (ISSN-L)
DOI: 10.3389/fimmu.2015.00015
PMC: PMC4306313
OpenAlex: W2027271725
Semantic Scholar: d2d3632814aa56e04fe85192b8fcd093a630672b
Cited by: 116
References: 127
Citations by year: 2026: 5 · 2025: 9 · 2024: 7 · 2023: 4 · 2022: 15 · 2021: 21 · 2020: 15 · 2019: 13 · 2018: 13 · 2017: 8 · 2016: 4 · 2015: 2
FWCI: 0.85
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Immunology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Funders: Fundação para a Ciência e a Tecnologia (SFRH/BD/84123/2012)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords: γδ T cells, receptor signaling, T cell activation, T cell differentiation, costimulatory receptors, CD27, CD28, cytokine receptors, interleukin-2 receptor, IL-7 receptor, IL-15 receptor, NK cell receptors, NKG2D, cytotoxicity, inhibitory receptors, PD-1, BTLA, T cell homeostasis, immunotherapy

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Five Layers of Receptor Signaling in Î³Î´ T-Cell Differentiation and Activation

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