γδ T cells develop, respond and survive - with a little help from CD27

Although the TNF receptor family member CD27 has been known for some time, its functional role as a coreceptor on T and B cells remains poorly understood. Recent reports have shown that CD27 and its ligand CD70 play a critical role in the development and function of γδ T cells in mice. In this issue of the European Journal of Immunology, a study now extends these findings to the Vγ9Vδ2(+) subset of human γδ T cells. This subset, whose responses are readily elicited by phosphoantigens, plays an important role in anti-tumor immune responses. This study shows that most Vγ9Vδ2(+) cells express CD27, and signaling via the CD27-CD70 axis is needed for their survival, proliferation and cytokine secretion. Moreover, CD27 functions as a coreceptor, which promotes, in conjunction with TCR-mediated signals, expansion of Th1-biased Vγ9Vδ2(+) cells. This new information underscores the significance of CD27 in γδ T-cell functional differentiation, and is likely to facilitate the development of γδ T-cell-based clinical immunotherapy.