β-lactam hypersensitivity involves expansion of circulating and skin-resident Th22 cells

sullivan, A, Wang, E, Farrell, J ORCID: 0000-0002-8726-5997, Whitaker, P, Faulkner, L, Peckham, D, Park, BK ORCID: 0000-0001-8384-824X and Naisbitt, D (2018) β-lactam hypersensitivity involves expansion of circulating and skin-resident Th22 cells. Journal of Allergy and Clinical Immunology, 141 (01). 235-249.E8.

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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 to 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 were explored. Naive 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/TH2 cytokines alongside IL-22 after 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 ligand 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 naive T cells from healthy volunteers also secreted IFN-γ, IL-13, IL-22, and cytolytic molecules. Aryl hydrocarbon receptor blockade prevented differentiation of the naive 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 naive T cells into antigen-specific TH22 cells is dependent on aryl hydrocarbon receptor signaling

Item Type:	Article
Uncontrolled Keywords:	Human, T cells, drug hypersensitivity
Depositing User:	Symplectic Admin
Date Deposited:	20 Feb 2017 12:45
Last Modified:	19 Jan 2023 07:19
DOI:	10.1016/j.jaci.2017.01.020
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3005440