Six-of-the-best: unique contributions of γδ T cells to immunology
Open accessAbstract
γδ T cells are a unique and conserved population of lymphocytes that have been the subject of a recent explosion of interest owing to their essential contributions to many types of immune response and immunopathology. But what does the integration of recent and long-established studies really tell us about these cells and their place in immunology? The time is ripe to consider the evidence for their unique and crucial functions. We conclude that whereas B cells and αβ T cells are commonly thought to contribute primarily to the antigen-specific effector and memory phases of immunity, γδ T cells are distinct in that they combine conventional adaptive features (inherent in their T cell receptors and pleiotropic effector functions) with rapid, innate-like responses that can place them in the initiation phase of immune reactions. This underpins a revised perspective on lymphocyte biology and the regulation of immunogenicity.
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The γδ T pool residing in a given tissue is the result of the wave of development from fetal to adult life, referred to as layered ontogeny.
“From further mouse studies, it is nonetheless becoming increasingly clearer that the γδ T pool residing in a given tissue is the result of the wave of development from fetal to adult life, referred to as layered ontogeny (8).”
From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [8]
In “Selective homing and retention” (page unavailable), the paper describes successive developmental waves homing to different mouse tissues, but says this explains tissue-localised compartments only “in part”; retention also matters. In “γδ T cells and ontogeny” (page unavailable), it says fetal-origin cells may persist into adulthood and combine with cells from postnatal progenitors. The claim overstates this qualified account as a settled explanation for the pool in any given tissue. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe double-negative T-cell fraction in the meninges has a high representation of γδ-TCR-expressing cells.
“Flow cytometric analysis revealed a high representation of γδ-T cell receptor (TCR)-expressing cells in the double-negative (DN) T-cell fraction (Extended Data Fig. 1a), a recently reported population in the meninges7,8.”
From Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons (2020) · cites this paper as [7]
Meningeal γδ T cells are linked to short-term memory via IL-17a signaling in glial cells.
“More recently, meningeal γδ T cells were linked to short-term memory via IL-17a signaling in glial cells7.”
From Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons (2020) · cites this paper as [7]
The finding that commensal-derived signals regulate IL-17a transcription by meningeal γδ17 cells is in disagreement with previously published work, which may have missed commensal participation by assessing IL-17a expression by ex vivo stimulation.
“This is in disagreement with the previously published work7, which may have missed the commensal participation by assessing IL-17a expression by ex vivo stimulation.”
From Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons (2020) · cites this paper as [7]
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- Authors
- Vantourout, P., & Hayday, A.
- Affiliations
- Cancer Research UK (GB)
- St Thomas' Hospital (GB)
- Corresponding author
- Hayday, Adrian
- Venue
- Nature Reviews Immunology
- Published
- 2013-01-25
- Volume
- 13
- Issue
- 2
- Pages
- 88-100
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC3951794
- OpenAlex
- W1512693074
- Cited by
- 1,232
- References
- 137
- Citations by year
- 2026: 68 · 2025: 81 · 2024: 82 · 2023: 80 · 2022: 97 · 2021: 121 · 2020: 112 · 2019: 95 · 2018: 112 · 2017: 102 · 2016: 83 · 2015: 79 · 2014: 79 · 2013: 40
- FWCI
- 8.17
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (085780)
- Cancer Research UK (19309)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Keywords
- γδ T cells, alpha beta T cells, T cell receptor, lymphocyte biology, immunopathology, immune response initiation, B cells
- MeSH terms
- Animals, Antigens, Humans, Immunity, Lymphocyte Activation, Protein Binding, T-Lymphocytes, Receptors, Antigen, T-Cell, gamma-delta
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