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Multiple drug hypersensitivity: normal Treg cell function but enhanced in vivo activation of drug-specific T cells.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2012
Author Daubner B, Groux-Keller M, Hausmann O V, Kawabata T, Naisbitt D J, Park B K, Wendland T, Lerch M, Pichler W J,
Project Investigating the primary immune response against drugs in humans
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Original article (peer-reviewed)

Journal Allergy
Volume (Issue) 67(1)
Page(s) 58 - 66
Title of proceedings Allergy
DOI 10.1111/j.1398-9995.2011.02720.x

Abstract

BACKGROUND   Up to 10% of patients with severe immune-mediated drug hypersensitivity reactions have tendencies to develop multiple drug hypersensitivities (MDH). The reason why certain individuals develop MDH and the underlying pathomechanism are unclear. We investigated different T cell subpopulations in MDH patients and compared them with patients allergic to a single drug and with healthy controls (HC). METHODS   We analyzed the in vitro reactivity of peripheral blood mononuclear cells from MDH patients (n=7), patients with hypersensitivity to a single drug (monoallergic, n=6), and healthy controls (HD) (n=6) to various drugs (mainly antibiotics and antiepileptics). By depleting and selectively re-adding CD4(+)  CD25(bright) T cells (T regulatory cells, Treg), their effect on drug-specific T cell reactivity was analyzed. The phenotype of reacting T cells was determined ex vivo by staining for markers of activation (CD38) and cell exhaustion (PD-1). RESULTS   No functional deficiency of Treg cells was observed in all drug-allergic patients. Drug-reactive T cells from MDH patients were found in the CD4(+) CD25(dim) T cell fraction and showed enhanced CD38 and PD-1 expression, while those from monoallergic patients reside in the resting CD4(+)  CD25(neg) T cell fraction. CONCLUSION   In patients with MDH, the drug-reactive T cells are contained in an in vivo pre-activated T cell fraction. Therefore, they may show a lower threshold for activation by drugs. The reason for this in vivo T cell pre-activation needs further investigations.
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