Publication: Enhancement of drug-specific lymphocyte proliferation using CD25 hi-depleted CD3+ effector cells
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2014-01-01
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14230097
10182438
10182438
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2-s2.0-84893652873
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Mahidol University
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SCOPUS
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International Archives of Allergy and Immunology. Vol.163, No.3 (2014), 198-205
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Yuttana Srinoulprasert, Werner J. Pichler Enhancement of drug-specific lymphocyte proliferation using CD25 hi-depleted CD3+ effector cells. International Archives of Allergy and Immunology. Vol.163, No.3 (2014), 198-205. doi:10.1159/000358491 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/34090
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Enhancement of drug-specific lymphocyte proliferation using CD25 hi-depleted CD3+ effector cells
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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/CD25hi) 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 CD25hi fraction were used as effector cells in the LTT. Irrelevant drugs were also included to determine specificity. 3H-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 CD25hi 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/CD25hi 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. © 2014 S. Karger AG, Basel.