Sullivan, A;
Wang, E;
Farrell, J;
Whitaker, P;
Faulkner, L;
Peckham, D;
Park, BK;
(2017)
β-Lactam hypersensitivity involves expansion of circulating and skin-resident TH22 cells.
Journal of Allergy and Clinical Immunology
, 141
(1)
235-249.e8.
10.1016/j.jaci.2017.01.020.
Preview |
Text
Faulkner Sullivan_1-s2.0-S0091674917302385-main (1).pdf - Accepted Version Download (2MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | β-Lactam hypersensitivity involves expansion of circulating and skin-resident TH22 cells |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jaci.2017.01.020 |
| Publisher version: | https://doi.org/10.1016/j.jaci.2017.01.020 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Human, T cells, drug hypersensitivity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10062613 |
Archive Staff Only
 |
View Item |
