γδ T cells: bridging innate and adaptive immunity in development, tissue residency, and disease
- 1Department of Pediatrics, the Second Hospital of Dalian Medical University
Abstract
γδ T cells are a unique lymphocyte lineage that bridges innate and adaptive immunity through MHC-unrestricted recognition of phosphoantigens, lipids, and stress-induced proteins. Their tissue-resident subsets, shaped by Vγ/Vδ chain usage, play essential roles in barrier surveillance, tissue homeostasis, and host defense.This review synthesizes recent advances that fundamentally reshape our understanding of γδ T cell biology. We highlight two conceptual frameworks: (1) dual recognition modalities of γδ TCRs, distinguishing structurally resolved ligand interactions from functionally supported recognition; and (2) a developmental wave model in which TCR signal strength and transcriptional networks program effector fates. Mouse and human studies are presented in dedicated species-specific sections and tables, with explicit attention to species-specific nomenclature and evidence levels.We cover γδ T cell development, tissue-resident programs, antigen recognition mechanisms (including butyrophilin-mediated phosphoantigen sensing, antibody-like foreign antigen recognition, and intracellular self-protein recognition), and the dual roles of γδ T cells in infection, cancer, and chronic inflammation. Therapeutic applications—adoptive transfer, CAR-engineered cells, and extracellular-vesicle vaccines—are critically appraised against current clinical evidence.Finally, we identify major unanswered questions: the complete γδ TCR ligand repertoire, the mechanisms maintaining tissue residency, and the translational gaps between mouse models and human disease. This review provides a structured framework for understanding γδ T cells as pivotal connectors of innate and adaptive immunity.
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BibTeX
@article{lou2026γδ,
title = {{γδ T cells: bridging innate and adaptive immunity in development, tissue residency, and disease}},
author = {Jiacheng Lou and Ning Zou},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1920627},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1920627/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - γδ T cells: bridging innate and adaptive immunity in development, tissue residency, and disease
AU - Jiacheng Lou
AU - Ning Zou
PY - 2026
DA - 2026/10/06
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1920627
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1920627/full
AB - γδ T cells are a unique lymphocyte lineage that bridges innate and adaptive immunity through MHC-unrestricted recognition of phosphoantigens, lipids, and stress-induced proteins. Their tissue-resident subsets, shaped by Vγ/Vδ chain usage, play essential roles in barrier surveillance, tissue homeostasis, and host defense.This review synthesizes recent advances that fundamentally reshape our understanding of γδ T cell biology. We highlight two conceptual frameworks: (1) dual recognition modalities of γδ TCRs, distinguishing structurally resolved ligand interactions from functionally supported recognition; and (2) a developmental wave model in which TCR signal strength and transcriptional networks program effector fates. Mouse and human studies are presented in dedicated species-specific sections and tables, with explicit attention to species-specific nomenclature and evidence levels.We cover γδ T cell development, tissue-resident programs, antigen recognition mechanisms (including butyrophilin-mediated phosphoantigen sensing, antibody-like foreign antigen recognition, and intracellular self-protein recognition), and the dual roles of γδ T cells in infection, cancer, and chronic inflammation. Therapeutic applications—adoptive transfer, CAR-engineered cells, and extracellular-vesicle vaccines—are critically appraised against current clinical evidence.Finally, we identify major unanswered questions: the complete γδ TCR ligand repertoire, the mechanisms maintaining tissue residency, and the translational gaps between mouse models and human disease. This review provides a structured framework for understanding γδ T cells as pivotal connectors of innate and adaptive immunity.
SN - 1664-3224
ER -