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

Autor: Daubner B, Groux-Keller M, Hausmann O V, Kawabata T, Naisbitt D J, Park B K, Wendland T, Lerch M, Pichler W J
Rok vydání: 2011
Předmět:
Zdroj: Allergy
ISSN: 1398-9995
Popis: 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.
Databáze: OpenAIRE