Mixing signals: molecular turn ons and turn offs for innate γδ T-cells

Lymphocytes of the gamma delta (gamma delta)-cell lineage are evolutionary conserved and although they express rearranged antigen-specific receptors, a large proportion respond as innate effectors. gamma delta T-cells are poised to combat infection by responding rapidly to cytokine stimuli similar to innate lymphoid cells. This potential to initiate strong inflammatory responses necessitates that inhibitory signals are balanced with activation signals. Here, we discuss some of the key mechanisms that regulate the development, activation, and inhibition of innate gamma delta T-cells in light of recent evidence that the inhibitory immunoglobulin-superfamily member B and T lymphocyte attenuator restricts their differentiation and effector function.