Mauri-Hellweg D, Bettens F, Mauri D, Brander C, Hunziker T, Pichler W J
Institute of Immunology and Allergology, Inselspital, Bern, Switzerland.
J Immunol. 1995 Jul 1;155(1):462-72.
To investigate how T cells are involved in hypersensitivity reactions to drugs that become immunogenic after metabolization, e.g., sulfonamides and antiepileptics, we analyzed in vitro the drug-induced activation of CD4+ and CD8+ T cell subsets, cytokine secretion, TCR V beta distribution, and proliferation of T cells from four drug-allergic individuals. In addition, the activation parameters CD25 and HLA-DR were analyzed in vivo on CD4+ and CD8+ T cells from five patients with acute drug allergies, some of them with anticonvulsant hypersensitivity syndrome with hepatitis. Our results show that, in vitro, drug-induced proliferation of PBMC from patients with allergy to sulfamethoxazole, phenytoin, or carbamazepine was specific and dose dependent. CD4+ as well as CD8+ T cells expressed elevated levels of CD25 and HLA-DR molecules after drug stimulation. Drug-activated lymphocytes secreted high amounts of IL-5 and normal or low levels of IL-2, IFN-gamma, IL-4, and TNF-alpha. An enhanced expansion of TCR V beta 17+ T cells 9 days after in vitro stimulation with sulfamethoxazole was observed in one patient with sulfamethoxazole allergy. The drug specificity of the in vitro-activated T cells was confirmed by generation of different sulfamethoxazole specific T cell lines and CD4+ and CD8+ T cell clones. T cell analysis of patients with acute drug allergy to carbamazepine, phenytoin, allopurinol, or paracetamol confirms the in vitro data, because all patients had activated CD4+ or CD8+ T cells in the circulation. Our data clearly show the involvement of drug-specific T cells in drug allergies.
为了研究T细胞如何参与对经代谢后具有免疫原性的药物（如磺胺类药物和抗癫痫药物）的超敏反应，我们在体外分析了来自四名药物过敏个体的药物诱导的CD4+和CD8+ T细胞亚群活化、细胞因子分泌、TCR Vβ分布以及T细胞增殖。此外，还对五名急性药物过敏患者（其中一些患有伴有肝炎的抗惊厥药超敏反应综合征）的CD4+和CD8+ T细胞进行了体内活化参数CD25和HLA-DR分析。我们的结果表明，在体外，对磺胺甲恶唑、苯妥英或卡马西平过敏患者的外周血单核细胞（PBMC）经药物诱导的增殖具有特异性且呈剂量依赖性。药物刺激后，CD4+以及CD8+ T细胞表达的CD25和HLA-DR分子水平升高。药物活化的淋巴细胞分泌大量IL-5以及正常或低水平的IL-2、IFN-γ、IL-4和TNF-α。在一名对磺胺甲恶唑过敏的患者中，观察到体外经磺胺甲恶唑刺激9天后TCR Vβ17+ T细胞的扩增增强。通过生成不同的磺胺甲恶唑特异性T细胞系以及CD4+和CD8+ T细胞克隆，证实了体外活化T细胞的药物特异性。对卡马西平、苯妥英、别嘌醇或对乙酰氨基酚急性药物过敏患者的T细胞分析证实了体外数据，因为所有患者循环中的CD4+或CD8+ T细胞均被活化。我们的数据清楚地表明药物特异性T细胞参与了药物过敏反应。
