Zanni M P, Mauri-Hellweg D, Brander C, Wendland T, Schnyder B, Frei E, von Greyerz S, Bircher A, Pichler W J
Institute of Immunology and Allergology, Inselspital, Bern, Switzerland.
J Immunol. 1997 Feb 1;158(3):1139-48.
To investigate the cellular immune response to the drug lidocaine, we generated T cell lines and clones from the peripheral blood of four patients with proven allergy to lidocaine. The patients had contact dermatitis after topical application of lidocaine, and local swelling or generalized erythema exudativum multiforme after submucosal/subcutaneous injection of lidocaine. Two of three lidocaine-specific T cell lines were oligoclonal and one even became monoclonal, while the simultaneously analyzed immune response to tetanus toxoid was polyclonal. The lidocaine-specific T cell lines cross-reacted to mepivacaine, but not to other local anesthetics (bupivacaine, procaine, oxybuprocaine, and tetracaine). The majority of reactive T cells belonged to the CD4 cell lineage and were MHC class II restricted, but cloning also revealed some MHC class I-restricted CD8+ clones. A total of 2 of 56 lidocaine-specific T cell clones were CD4-CD8- and expressed TCR-gammadelta. The majority of 13 analyzed CD4 clones produced a rather polarized cytokine pattern, with a dominance of Th2-like cytokines showing a high IL-5 production. In addition, three CD4+ and all CD8+ (n = 7) clones secreted high IFN-gamma and low levels of IL-5/IL-4 (Th1-like). The data illustrate that a drug that sensitizes via the skin elicits a heterogeneous T cell response. The high IL-5 production and the participation of specific CD4+CD8+ and even gammadelta+ T cells appear to be distinguishing features of this hapten-specific immune response.
为了研究对利多卡因药物的细胞免疫反应,我们从四名已证实对利多卡因过敏的患者外周血中生成了T细胞系和克隆。这些患者在局部应用利多卡因后出现接触性皮炎,在黏膜下/皮下注射利多卡因后出现局部肿胀或全身性多形性红斑渗出。三个利多卡因特异性T细胞系中有两个是寡克隆的,其中一个甚至变成了单克隆,而同时分析的对破伤风类毒素的免疫反应是多克隆的。利多卡因特异性T细胞系与甲哌卡因发生交叉反应,但与其他局部麻醉剂(布比卡因、普鲁卡因、奥布卡因和丁卡因)无交叉反应。大多数反应性T细胞属于CD4细胞谱系,受MHC II类分子限制,但克隆也揭示了一些受MHC I类分子限制的CD8+克隆。56个利多卡因特异性T细胞克隆中有2个是CD4-CD8-,并表达TCR-γδ。在分析的13个CD4克隆中,大多数产生了相当极化的细胞因子模式,以Th2样细胞因子为主,IL-5产生量高。此外,三个CD4+和所有CD8+(n = 7)克隆分泌高水平的IFN-γ和低水平的IL-5/IL-4(Th1样)。数据表明,一种通过皮肤致敏的药物会引发异质性T细胞反应。高IL-5产生以及特定CD4+CD8+甚至γδ+ T细胞的参与似乎是这种半抗原特异性免疫反应的显著特征。