A Novel Type of Cell Death of Lymphocytes Induced by mAb

单克隆抗体诱导的新型淋巴细胞细胞死亡

• 批准号: 09670343
• 负责人: MATSUOKA Shuji
• 金额: $ 1.98万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670343/
• 关键词: RE2; MHC class I; apoptosis; perforin; cell death; Fulminant Hepatitis

A Novel Type of Cell Death of Lymphocytes Induced by mAbWe have established a rat anti-mouse mAb, RE2, which recognizes an epitope that is on an MHC class I monomorphic region. RE2 mAb killed activated lymphocytes and leukemic cell lines in the absence of complement. Electromicroscopically, formation of Giant holes was found on the cell membrane of RE2-treated cells. There was no indication of DNA fragmentation nor swelling of mitochondria during the cell lysis, suggesting that the cell death is not due to apoptosis or typical necrosis. We investigated the effect of RE2 mAb on lymphocytes from autoimmune disease prone NZB/W Fl mice. BI cells in the peritoneal cavity and spleen were drastically eliminated by treatment with RE2 both in vivo and in vitro. In the other experiment, We also investigated the effect of RE2 mAb on Con A induced hepatitis. RE2 completely inhibited the elevation of serum GOT and GPT of the hepatitis induced mouse. RE2 mAb kills only activated lymphocytes but resting cells, it may help us to develop a therapeutic device for autoimmune diseases, Fulminant Hepatitis and lymphom as.

单抗诱导淋巴细胞死亡的一种新类型我们已经建立了一种大鼠抗小鼠单抗RE2，它识别MHC I类单态区上的一个表位。在缺乏补体的情况下，RE2单抗可杀伤活化的淋巴细胞和白血病细胞系。在电子显微镜下，RE2处理的细胞膜上形成了巨大的孔洞。在细胞裂解过程中未见DNA断裂或线粒体肿胀的迹象，提示细胞死亡不是由于细胞凋亡或典型的坏死。我们研究了RE2单抗对易患自身免疫病的NZB/WF1小鼠淋巴细胞的影响。在体内和体外，RE2均能显著消除小鼠腹膜和脾中的BI细胞。在另一项实验中，我们还观察了RE2单抗对ConA诱导的肝炎的影响。RE2可完全抑制肝炎小鼠血清GOT、GPT的升高。RE2单抗只能杀死活化的淋巴细胞，而不能杀死静息细胞，这可能有助于我们开发一种治疗自身免疫性疾病、重型肝炎和淋巴瘤AS的装置。

项目成果

Shuji Matsuoka et al.: "A Novel type of cell death of lymphocytes Induced by a monoclonal antibody without participation of complement." J.Exp.Med.Vol.181. 2007-2015 (1995)

Shuji Matsuoka 等人：“一种由单克隆抗体诱导的新型淋巴细胞死亡，无需补体参与。”