PHYSIOLOGICAL ROLES OF GAMMA DELTA T CELLS: FROM IMMUNITY TO CLINICAL APPLICATIONS

Gamma delta (γδ) T cells represent a unique subset of lymphocytes that bridge innate and adaptive immunity through their ability to recognize stress-induced ligands in a major histocompatibility complex independent manner.Distributed primarily at epithelial barriers, these cells function as sentinels against infection and malignant transformation while simultaneously contributing to tissue repair and homeostasis.Functionally, γδ T cells are highly versatile: they produce pro-inflammatory cytokines such as interferon-γ (IFN-γ) and interleukin-17 (IL-17), mediate direct cytotoxicity, and, under certain conditions, exert regulatory roles by secreting interleukin-10 (IL-10) and transforming growth factor-β (TGF-β).This dual capacity allows them to either protect against pathogens and tumors or contribute to chronic inflammation and autoimmunity.Recent advances have highlighted the clinical significance of γδ T cells across a broad spectrum of diseases, including cancer, infectious, autoimmune disorders, metabolic and cardiovascular conditions, and pregnancy-related complications.Moreover, their potential as biomarkers and therapeutic targets has been demonstrated through adoptive transfer, in vivo activation, and genetic engineering approaches.Despite this promise, the plasticity of γδ T cells presents challenges, as the same subsets that confer protection in one context may exacerbate pathology in another.A deeper understanding of their biology and microenvironmental regulation is therefore essential for harnessing their therapeutic potential.This review summarizes the current knowledge of the physiological roles of γδ T cells across tissues and disease states, emphasizing their translational relevance and opportunities for clinical application.