ReviewFrontiers in immunology2026
γδ T cells: bridging innate and adaptive immunity in development, tissue residency, and disease.
Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 authors.
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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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