Tissue-intrinsic γδ T cells critically regulate Tissue-Resident Memory CD8 T cells

Summary

Because Tissue-Resident Memory T (T RM ) cells contribute critically to body-surface immunoprotection and/or immunopathology in multiple settings, their regulation is biologically and clinically important. Interestingly, T RM commonly develop in epithelia part-shaped by innate-like lymphocytes that become tissue-intrinsic during development. Here we show that polyclonal T RM cells induced by allergic contact dermatitis (ACD) interact with signature intraepidermal γδ T cells, facilitating a feedback-loop wherein T RM -derived IFNγ upregulates PD-L1 on γδ cells that can thereupon regulate PD1 + T RM . Thus, T RM induced by ACD in mice lacking either local γδ cells, or lacking a single gene (IFNγR) expressed by local γδ cells, displayed enhanced proliferative and effector potentials. Those phenotypes were associated with strikingly limited motility, reduced T RM quality. and an impaired capacity to restrain melanoma. Thus, inter-individual and tissue-specific variation in how tissue-intrinsic lymphocytes integrate with T RM may sit upstream of variation in responses to cancer, allergens and other challenges, and may likewise underpin inflammatory pathologies repeatedly observed in γδ-deficient animals.

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