The DOI matches its Crossref record; 126 of the 127 references it cites were found in a registry or an index.
Five Layers of Receptor Signaling in γδ T-Cell Differentiation and Activation
Open accessAbstract
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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“IL-12 and IL-18 promote IFN-γ production, while IL-1β and IL-23 drive them towards IL-17-producing cells (14).”
From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [14]
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1 retracted
IL-21 Regulates the Differentiation of a Human γδ T Cell Subset Equipped with B Cell Helper Activity
Caccamo, N., Todaro, M., Manna, M. P. L., Sireci, G., Stassi, G., & Dieli, F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041940 · Cited by 64
RetractedSmith-Garvin, J. E., Koretzky, G. A., & Jordan, M. S. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132706 · Cited by 2,144
CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms
Parry, R. V., Chemnitz, J. M., Frauwirth, K. A., Lanfranco, A. R., Braunstein, I., Kobayashi, S. V., Linsley, P. S., Thompson, C. B., & Riley, J. L. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9543-9553.2005 · Cited by 1,931
Sutton, C. E., Lalor, S. J., Sweeney, C. M., Brereton, C. F., Lavelle, E. C., & Mills, K. H. G. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.001 · Cited by 1,553
The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor
Gasser, S., Orsulic, S., Brown, E. J., & Raulet, D. H. (2005) · Nature · doi:10.1038/nature03884 · Cited by 1,308
Controlling Natural Killer Cell Responses: Integration of Signals for Activation and Inhibition
Long, E. O., Kim, H. S., Liu, D., Peterson, M., & Rajagopalan, S. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075005 · Cited by 1,258
Chemnitz, J. M., Parry, R. V., Nichols, K. E., June, C. H., & Riley, J. L. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.2.945 · Cited by 1,246
Interleukin-2 at the Crossroads of Effector Responses, Tolerance, and Immunotherapy
Liao, W., Lin, J., & Leonard, W. J. (2013) · Immunity · doi:10.1016/j.immuni.2013.01.004 · Cited by 1,107
Regulation of Cutaneous Malignancy by γδ T Cells
Girardi, M., Oppenheim, D. E., Steele, C. R., Lewis, J. M., Glusac, E. J., Filler, R. B., Hobby, P., Sutton, B. J., Tigelaar, R. E., & Hayday, A. (2001) · Science · doi:10.1126/science.1063916 · Cited by 1,068
Natural and synthetic non-peptide antigens recognized by human γδ T cells
Tanaka, Y., Morita, C. T., Tanaka, Y., Nieves, E., Brenner, M. B., & Bloom, B. R. (1995) · Nature · doi:10.1038/375155a0 · Cited by 1,003
Research works printed but not linked: 1
- Biswas, 2000, Engagement of CD30 shapes the secretion of cytokines by human gamma delta T cells, Eur J Immunol, 30, 2172, 10.1002/1521-4141(2000)30:182172::aid-immu21723.0.co;2-5 · DOI
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Hoque, M., Grigg, J. B., Ramlall, T. F., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.19.604350
Anderson, J., Nair, G., & Barisa, M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21766-1.00008-4
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“Accumulating evidence indicates that signaling derived from the TCR and NKG2D can act in concert in gd T cells (171).”
Hung, M., Lin, H., Li, Y.-H., Cho, D., Chiu, S., Pan, C., Huang, S.-W., Fang, H.-Y., Chen, Y.-W., Kan, K., et al. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.117115 · Cited by 1
Metadata
- 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)
- 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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