Beeler A

Cavani A

Daubner B

Khalili B

Lochmatter P

Mayorga C

Pichler WJ

Schnyder B

Srinoulprasert Y

Tang YH

Torres MJ

Werner J. Pichler

Yuttana Srinoulprasert

Zawodniak A

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; 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&lt;sup&gt;hi&lt;/sup&gt;) from in vitro stimulated cell cultures was previously reported to be a promising method to increase the sensitivity of proliferation tests. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; The aim of this investigation is to evaluate the effect of removal of regulatory T cells on the sensitivity of the LTT. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Patients with well-documented drug hypersensitivity were recruited. Peripheral blood mononuclear cells, isolated CD3&lt;sup&gt;+&lt;/sup&gt; and CD3&lt;sup&gt;+&lt;/sup&gt; T cells depleted of the CD25&lt;sup&gt;hi&lt;/sup&gt; fraction were used as effector cells in the LTT. Irrelevant drugs were also included to determine specificity. &lt;sup&gt;3&lt;/sup&gt;H-thymidine incorporation was utilized as the detection system and results were expressed as a stimulation index (SI). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; 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&lt;sup&gt;hi&lt;/sup&gt; fraction, which was FOXP3&lt;sup&gt;+&lt;/sup&gt; 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. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Removal of Treg/CD25&lt;sup&gt;hi&lt;/sup&gt; 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.</jats:p

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International Archives of Allergy and Immunology

Enhancement of Drug-Specific Lymphocyte Proliferation Using CD25&lt;sup&gt;hi&lt;/sup&gt;-Depleted CD3&lt;sup&gt;+&lt;/sup&gt; Effector Cells

Enhancement of Drug-Specific Lymphocyte Proliferation Using CD25<sup>hi</sup>-Depleted CD3<sup>+</sup> Effector Cells

Enhancement of Drug-Specific Lymphocyte Proliferation Using CD25<sup>hi</sup>-Depleted CD3<sup>+</sup> Effector Cells

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