Regulatory Functions of γδ T Cells

γδ T cells account for approximately 5% of peripheral blood T cells but are more abundant in mucosal tissue. Based on the recognized ligands and their general lack of MHC restriction, γδ T cells are considered as unconventional T cells that link innate and adaptive immunity. γδ T cells produce a diverse range of cytokines, exert cytotoxic effector function, can act as antigen-presenting cells, and display regulatory activity. Here we review the current knowledge on the regulatory functions of murine and human γδ T cells. Some γδ T cells produce inhibitory cytokines such as transforming growth factor-β but γδ T cells can utilize additional regulatory mechanisms. By subverting regulatory T cells (Treg) through induction of Treg apoptosis or cytokine-dependent reversal of Treg activity, however, γδ T cells can also enhance effector T cell activity and thereby contribute to autoimmunity. A more precise understanding of the plasticity of regulatory γδ T cells is required to specifically identify strategies for intentional modulation of their beneficial or detrimental regulatory activity.