Sullivan, A, Wang, E, Farrell, J et al. (5 more authors) (2018) β-lactam hypersensitivity involves expansion of circulating and skin-resident Th22 cells. Journal of Allergy and Clinical Immunology, 141 (1). pp. 235-249. ISSN 0091-6749
Abstract
Background: β-lactam hypersensitivity has been classified according to the phenotype and function of drug-specific T-cells; however, new T-cell subsets have not been considered. Objective: The objective of this study was use piperacillin as a model of β-lactam hypersensitivity to study the nature of the drug-specific T-cell response induced in the blood and skin of hypersensitive patients and healthy volunteers. Methods: Drug-specific T-cells were cloned from blood and inflamed skin and cellular phenotype and function was explored. Naïve T cells from healthy volunteers were primed to piperacillin, cloned and subjected to the similar analyses. Results: PBMC and T-cell clones (n=570, 84% CD4+) from blood of piperacillin hypersensitive patients proliferated and secreted Th1/2 cytokines alongside IL-22 following drug stimulation. IL-17A secretion was not detected. Drug-specific clones from inflamed skin (n=96, 83% CD4+) secreted a similar profile of cytokines, but displayed greater cytolytic activity, secreting perforin, granzyme B and Fas L when activated. Blood- and skin-derived clones expressed high levels of skin-homing chemokine receptors and migrated in the presence of the ligands CCL17 and CCL27. Piperacillin-primed naïve T-cells from healthy volunteers also secreted IFN-γ, IL-13, IL-22 and cytolytic molecules. Aryl hydrocarbon (ArH) receptor blockade prevented differentiation of the naïve T-cells into antigen-specific Il-22 secreting cells. Conclusion: Together our results reveal that circulating and skin resident antigen-specific IL-22 secreting T-cells are detectable in patients with β-lactam hypersensitivity. Furthermore, differentiation of naïve T-cells into antigen-specific Th22 cells is dependent on ArH receptor signalling.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 American Academy of Allergy, Asthma & Immunology. This is an author produced version of a paper published in Journal of Allergy and Clinical Immunology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Human; T-cells; drug hypersensitivity |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Translational Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 23 Feb 2017 10:17 |
Last Modified: | 05 Jul 2018 10:16 |
Published Version: | https://doi.org/10.1016/j.jaci.2017.01.020 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jaci.2017.01.020 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:112731 |