γδ T Cell Update: Adaptate Orchestrators of Immune Surveillance

As interest in γδ T cells grows rapidly, what key points are emerging, and where is caution warranted? γδ T cells fulfill critical functions, as reflected in associations with vaccine responsiveness and cancer survival in humans and ever more phenotypes of γδ T cell-deficient mice, including basic physiological deficiencies. Such phenotypes reflect activities of distinct γδ T cell subsets, whose origins offer interesting insights into lymphocyte development but whose variable evolutionary conservation can obfuscate translation of knowledge from mice to humans. By contrast, an emerging and conserved feature of γδ T cells is their "adaptate" biology: an integration of adaptive clonally-restricted specificities, innate tissue-sensing, and unconventional recall responses that collectively strengthen host resistance to myriad challenges. Central to adaptate biology are butyrophilins and other γδ cell regulators, the study of which should greatly enhance our understanding of tissue immunogenicity and immunosurveillance and guide intensifying clinical interest in γδ cells and other unconventional lymphocytes.