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Inflammatory response and regulatory mechanism in drug allergy.

药物过敏的炎症反应及调节机制。

基本信息

批准号：
17591168
负责人：
HASHIZUME Hideo
金额：
$ 2.24万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591168/
关键词：
Drug allergy Drug-induced hypersensitivity syndrome T cell Chemokine Herpes virus Cytotoxic T cell Regulatory T cell 細胞傷害性T細胞薬剤過敏症候群薬剤反応性T細胞ヘルペスウィルス cytopathic effect

项目摘要

Analysis of feature of T cell that recognizes drug as antigen1.Drug-specific T cell clone or the line was established from the peripheral blood from three patients with drug-induced hypersensitive syndrome and one patient with pustulat type of gold-induced drug erutption and their phenotypes, producing cytokines and chemokine receptors were examined.2.We also confirmed functional expressions of chemokine receptors of these cells by TAXSCAN.Analysis of regulatory T cells in drug allergy1.Especially, it was found to the first stage of the sickness for the number of CD25 positivity CD4 positivity cells to increase, and to decrease rapidly afterwards from the examination of Fenotaip of a peripheral blood the passing time in three patients of the medicine irritability syndrome. Moreover, because the time of the reinvigoration of the herpes virus in the peak of this increase and this patient is almost corresponding, this cell has the possibility to be related to the activation of the herpesvirus that induces the immunity control besides taking part in the appearance of disease of the drug eruption and conceals oneself.2. We could obtain a large number of lymphocytes derived skin from a patient with drug-induced hypersensitivity syndrome. Therefore, we further examined on these cells. We labeled these cells with Cr and investigated cytotoxicity of the PBMC against the skin-derived cells by Cr-release assay. Interestingly, the patient's PBMC had significant cytotoxicity against the skin-derived cells, which was completely blocked with anti-MHC-class I Ab, suggesting circulating CD8+ cells target the skin-infiltrating cells. We could not any infection of EBV, CMV, HHV-6, HHV-7 or HHV-8 by nested PCR method in these cells. This suggests that regulatory mechanism had been lost after elicitation of drug allergy, implicating changing in immune regulatory system during drug allergy.

识别药物为抗原的T细胞特性分析1.从3例药物过敏综合征和1例脓疱型金诱导药物过敏患者的外周血中建立了药物特异性T细胞克隆或系，2.通过TAXSCAN分析证实了这些细胞的趋化因子受体的功能性表达。特别是3例药物过敏综合征患者外周血中的非诺泰检测发现，在发病初期，CD_（25）+CD_（4）+细胞数增加，随后迅速下降。此外，由于该增加高峰期疱疹病毒复活的时间与该患者几乎一致，该细胞除了参与药疹疾病的出现和隐藏自身外，还可能与诱导免疫控制的疱疹病毒的激活有关.我们可以从药物过敏综合征患者的皮肤中获得大量的淋巴细胞。因此，我们对这些细胞进行了进一步的研究。我们用Cr标记这些细胞，并通过Cr释放测定研究PBMC对皮肤来源的细胞的细胞毒性。有趣的是，患者的PBMC对皮肤来源的细胞具有显著的细胞毒性，其被抗MHC-I类Ab完全阻断，表明循环CD 8+细胞靶向皮肤浸润细胞。巢式PCR检测未发现EBV、CMV、HHV-6、HHV-7、HHV-8感染。提示药物过敏后免疫调节机制丧失，提示药物过敏时免疫调节系统发生变化。