Enhancement of drug-specific lymphocyte proliferation using CD25(hi)-depleted CD3(+) effector cells.

Abstract:

BACKGROUND:The lymphocyte transformation test (LTT) is used for in vitro diagnosis of drug hypersensitivity reactions. While its specificity is over 90%, sensitivity is limited and depends on the type of reaction, drug and possibly time interval between the event and analysis. Removal of regulatory T cells (Treg/CD25(hi)) from in vitro stimulated cell cultures was previously reported to be a promising method to increase the sensitivity of proliferation tests. OBJECTIVE:The aim of this investigation is to evaluate the effect of removal of regulatory T cells on the sensitivity of the LTT. METHODS:Patients with well-documented drug hypersensitivity were recruited. Peripheral blood mononuclear cells, isolated CD3(+) and CD3(+) T cells depleted of the CD25(hi) fraction were used as effector cells in the LTT. Irrelevant drugs were also included to determine specificity. (3)H-thymidine incorporation was utilized as the detection system and results were expressed as a stimulation index (SI). RESULTS:SIs of 7/11 LTTs were reduced after a mean time interval of 10.5 months (LTT 1 vs. LTT 2). Removal of the CD25(hi) fraction, which was FOXP3(+) and had a suppressive effect on drug-induced proliferation, resulted in an increased response to the relevant drugs. Sensitivity was increased from 25 to 82.35% with dramatically enhanced SI (2.05 to 6.02). Specificity was not affected. CONCLUSION:Removal of Treg/CD25(hi) cells can increase the frequency and strengths of drug-specific proliferation without affecting specificity. This approach might be useful in certain drug hypersensitivity reactions with borderline responses or long time interval since the hypersensitivity reaction.

authors

Srinoulprasert Y,Pichler WJ

doi

10.1159/000358491

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

198-205

issue

3

eissn

1018-2438

issn

1423-0097

pii

000358491

journal_volume

163

pub_type

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