T cell receptor γδ is a critical, real-time determinant of unique tissue surveillance mechanisms
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γδ T cells are mediators of immunosurveillance used in the clinic. However, their status remains paradoxical. While many display overt traits of adaptive immunity, several major γδ cell subsets including those in barrier tissues make rapid, seemingly TCR-independent responses phenocopying innate lymphoid cells (ILC). While such uncertainty exists, the requirements for γδ T cell-mediated immunosurveillance will remain unclear. This study resolves the paradox, showing that tissue-intrinsic γδ T cells share an absolute real-time dependence on the TCR for their phenotypes, including so-called innate responses to tissue stress and carcinogenesis. While different tissue-intrinsic γδ subsets showed distinct TCR-dependencies, we identified a shared set of TCR-regulated molecules that was likewise disrupted by acute TCR ablation in human γδ T cells. These findings unequivocally distinguish γδ cells from ILC and establish that immunosurveillance by γδ T cells requires an environment conducive to TCR signalling.[139]
