IFN-γ–dependent interactions between tissue-intrinsic γδ T cells and tissue-infiltrating CD8 T cells limit allergic contact dermatitis

Elicitation of allergic contact dermatitis (ACD), an inflammatory type 4 hypersensitivity disease, induces skin infiltration by polyclonal effector CD8 αβ T cells and precursors of tissue-resident memory T (TRM) cells. Because TRM have long-term potential to contribute to body-surface immunoprotecti...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2023-12, Vol.152 (6), p.1520-1540
Main Authors: Muñoz-Ruiz, Miguel, Llorian, Miriam, D'Antuono, Rocco, Pavlova, Anna, Mavrigiannaki, Anna Maria, McKenzie, Duncan, García-Cassani, Bethania, Iannitto, Maria Luisa, Wu, Yin, Dart, Robin, Davies, Daniel, Jamal-Hanjani, Mariam, Jandke, Anett, Ushakov, Dmitry S., Hayday, Adrian C.
Format: Article
Language:English
Subjects:
Animals
B7-H1 Antigen
CD8-Positive T-Lymphocytes - pathology
Dermatitis, Allergic Contact - pathology
Humans
IFN-γ
Interferon-gamma
Mice
PD-L1
Skin - pathology
tissue immuno-ecology
Tissue-intrinsic innate-like lymphocytes
tissue-resident memory T cells
γδ T cells
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Summary:Elicitation of allergic contact dermatitis (ACD), an inflammatory type 4 hypersensitivity disease, induces skin infiltration by polyclonal effector CD8 αβ T cells and precursors of tissue-resident memory T (TRM) cells. Because TRM have long-term potential to contribute to body-surface immunoprotection and immunopathology, their local regulation needs a fuller understanding. We sought to investigate how TRM-cell maturation might be influenced by innate-like T cells pre-existing within many epithelia. This study examined CD8+ TRM-cell maturation following hapten-induced ACD in wild-type mice and in strains harboring altered compartments of dendritic intraepidermal γδ T cells (DETCs), a prototypic tissue-intrinsic, innate-like T-cell compartment that reportedly regulates ACD, but by no elucidated mechanism. In addition to eliciting CD8 TRM, ACD induced DETC activation and an intimate coregulatory association of the 2 cell types. This depended on DETC sensing IFN-γ produced by CD8 cells and involved programmed death-ligand 1 (PD-L1). Thus, in mice lacking DETC or lacking IFN-γ receptor solely on γδ cells, ACD-elicited CD8 T cells showed enhanced proliferative and effector potentials and reduced motility, collectively associated with exaggerated ACD pathology. Comparable dysregulation was elicited by PD-L1 blockade in vitro, and IFN-γ–regulated PD-L1 expression was a trait of human skin-homing and intraepithelial γδ T cells. The size and quality of the tissue-infiltrating CD8 T-cell response during ACD can be profoundly regulated by local innate-like T cells responding to IFN-γ and involving PD-L1. Thus, interindividual and tissue-specific variations in tissue-intrinsic lymphocytes may influence responses to allergens and other challenges and may underpin inflammatory pathologies such as those repeatedly observed in γδ T-cell–deficient settings.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2023.07.015