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Cited by 96T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisIL-33, ST2, and ILC Pathways

Human γδ T-Cell Control of Mucosal Immunity and Inflammation

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McCarthy, Neil E., Eberl, Matthias·2018·Frontiers in Immunology
DOI 10.3389/fimmu.2018.00985PMC PMC5949325
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Abstract

Human γδ T-cells include some of the most common ‘antigen-specific’ cell types in peripheral blood and are enriched yet further at mucosal barrier sites where microbial infection and tumors often originate. While the γδ T-cell compartment includes multiple subsets with highly flexible effector functions, human mucosal tissues are dominated by host stress-responsive Vδ1+ T-cells and microbe-responsive Vδ2+ T-cells. Widely recognized for their potent cytotoxicity, emerging data suggest that γδ T-cells also exert strong influences on downstream adaptive immunity to pathogens and tumors, in particular via activation of antigen-presenting cells and/or direct stimulation of other mucosal leukocytes. These unique functional attributes and lack of MHC restriction have prompted considerable interest in therapeutic targeting of γδ T-cells. Indeed, several drugs already in clinical use including vedolizumab, infliximab, and azathioprine likely owe their efficacy in part to modulation of γδ T-cell function. Recent clinical trials of Vδ2+ T-cell-selective treatments indicate a good safety profile in human patients, and efficacy is set to increase as more potent/targeted drugs continue to be developed. Key advances will include identifying methods of directing γδ T-cell recruitment to specific tissues to enhance host protection against invading pathogens, or alternatively, retaining these cells in the circulation to limit peripheral inflammation and/or improve responses to blood malignancies. Human γδ T-cell control of mucosal immunity is likely exerted via multiple mechanisms including activation of antigen-presenting cells and direct stimulation of tissue-resident leukocytes. Understanding the microenvironmental signals that regulate these functions will be critical to the development of new γδ T-cell-based therapies.

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  • Vδ2 is the largest subset of circulating human γδ T cells in the blood, which gets rapidly recruited to the mucosal surface to participate in the clearance of localized infection.

    “Vδ2 is the largest subset of circulating human γδ T cells in the blood, which gets rapidly recruited to the mucosal surface to participate in the clearance of localized infection (17).”

    From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [17]

    The section “γδ T-Cells Stimulate Complex Mucosal Leukocyte Responses” (page unavailable) says Vδ2+ cells are rapidly recruited to mucosal tissues in higher primates and mediate protection against bacteria in humanized mice. It does not establish that Vδ2+ cells are the largest subset of circulating human γδ T cells, and the recruitment and protection findings come from different models. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
McCarthy, N. E., & Eberl, M.
Affiliations
  • Queen Mary University of London (GB)
  • Cardiff University (GB)
Corresponding author
McCarthy, Neil E.
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2018-05-07
Volume
9
Pages
985-985
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2018.00985
PMC
PMC5949325
OpenAlex
W2800986973
Cited by
96
References
3
Citations by year
2026: 10 · 2025: 6 · 2024: 10 · 2023: 12 · 2022: 21 · 2021: 17 · 2020: 8 · 2019: 9 · 2018: 3
FWCI
0.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (AC1120IF06)
  • Crohn’s and Colitis UK (M/13/5)
  • Crohn’s in Childhood Research Association
  • Medical Research Council (MR/N023145/1, MR/R008302/1)
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 › IL-33, ST2, and ILC Pathways
Keywords
γδ T cells, mucosal immunity, Vδ1 T cells, Vδ2 T cells, inflammation, antigen-presenting cells, adaptive immunity, vedolizumab, infliximab, azathioprine, hematologic malignancies
MeSH terms
Intraepithelial Lymphocytes, Antigen-Presenting Cells, Cell Differentiation, Clinical Trials as Topic, Humans, Inflammation, Interferon-gamma, Lymphocyte Activation, Neoplasms, Immunity, Mucosal

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