Differentiation and functional plasticity of gamma-delta (γδ) T cells under homeostatic and disease conditions

• Gamma-delta (γδ) T cells are present at a higher frequency at epithelial and mucosal barriers. • Depending on the tissue microenvironment, γδ T cells show regulatory and effector cell function. • Plasticity of γδ T cells differentiation in the tissue microenvironment help in the diverse functions. • Contact-dependent and -independent interaction of γδ T cells with other immune cells shape the effector immune response. Gamma-delta (γδ) T cells are a heterogeneous population of immune cells, which constitute <5% of total T cells in mice lymphoid tissue and human peripheral blood. However, they comprise a higher proportion of T cells in the epithelial and mucosal barrier, where they perform immune functions, help in tissue repair, and maintaining homeostasis. These tissues resident γδ T cells possess properties of innate and adaptive immune cells which enables them to perform a variety of functions during homeostasis and disease. Emerging data suggest the involvement of γδ T cells during transplant rejection and survival. Interestingly, several functions of γδ T cells can be modulated through their interaction with other immune cells. This review provides an overview of development, differentiation plasticity into regulatory and effector phenotypes of γδ T cells during homeostasis and various diseases.