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

Publication date: Available online 20 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Andrew Sullivan, Eryi Wang, John Farrell, Paul Whitaker, Lee Faulkner, Daniel Peckham, B. Kevin Park, Dean J. Naisbitt
Backgroundβ-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.ObjectiveThe 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.MethodsDrug-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.ResultsPBMC 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.ConclusionTogether 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.

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Capsule summary: New T-cell subsets have not been considered in the context of drug hypersensitivity. Herein, we show that antigen-specific circulating and skin resident CD4+ and CD8+ T-cells secrete IL-22 and cytolytic molecules following drug treatment.


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