γδ T Cell Update: Adaptate Orchestrators of Immune Surveillance

As interest in gamma delta T cells grows rapidly, what key points are emerging, and where is caution warranted? gamma delta T cells fulfill critical functions, as reflected in associations with vaccine responsiveness and cancer survival in humans and ever more phenotypes of gamma delta T cell-deficient mice, including basic physiological deficiencies. Such phenotypes reflect activities of distinct gamma delta 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 gamma delta 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 gamma delta cell regulators, the study of which should greatly enhance our understanding of tissue immunogenicity and immunosurveillance and guide intensifying clinical interest in gamma delta cells and other unconventional lymphocytes.