| First Author | Muñoz-Ruiz M | Year | 2023 |
| Journal | J Allergy Clin Immunol | Volume | 152 |
| Issue | 6 | Pages | 1520-1540 |
| PubMed ID | 37562754 | Mgi Jnum | J:350478 |
| Mgi Id | MGI:7663332 | Doi | 10.1016/j.jaci.2023.07.015 |
| Citation | Munoz-Ruiz M, et al. (2023) IFN-gamma-dependent interactions between tissue-intrinsic gammadelta T cells and tissue-infiltrating CD8 T cells limit allergic contact dermatitis. J Allergy Clin Immunol 152(6):1520-1540 |
| abstractText | BACKGROUND: Elicitation of allergic contact dermatitis (ACD), an inflammatory type 4 hypersensitivity disease, induces skin infiltration by polyclonal effector CD8 alphabeta T cells and precursors of tissue-resident memory T (T(RM)) cells. Because T(RM) have long-term potential to contribute to body-surface immunoprotection and immunopathology, their local regulation needs a fuller understanding. OBJECTIVE: We sought to investigate how T(RM)-cell maturation might be influenced by innate-like T cells pre-existing within many epithelia. METHODS: This study examined CD8(+) T(RM)-cell maturation following hapten-induced ACD in wild-type mice and in strains harboring altered compartments of dendritic intraepidermal gammadelta T cells (DETCs), a prototypic tissue-intrinsic, innate-like T-cell compartment that reportedly regulates ACD, but by no elucidated mechanism. RESULTS: In addition to eliciting CD8 T(RM), ACD induced DETC activation and an intimate coregulatory association of the 2 cell types. This depended on DETC sensing IFN-gamma produced by CD8 cells and involved programmed death-ligand 1 (PD-L1). Thus, in mice lacking DETC or lacking IFN-gamma receptor solely on gammadelta 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-gamma-regulated PD-L1 expression was a trait of human skin-homing and intraepithelial gammadelta T cells. CONCLUSIONS: 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-gamma 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 gammadelta T-cell-deficient settings. |
