Anti-TOSO antibody treatment promotes T cell activation-induced cell death (AICD) in vitro and in vivo
Anti-TOSO antibody treatment promotes T cell activation-induced cell death (AICD) in vitro and in vivo
复制标题
抗 TOSO 抗体治疗在体外和体内促进 T 细胞活化诱导的细胞死亡 (AICD)
DOI：
10.1007/s11434-014-0132-x
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发表时间：
2014-03
影响因子：
--
通讯作者：
shengdian wang
中科院分区：
文献类型：
--
作者：
yi tan;xue han;xiaoran wu;qiao xing;lieping chen;shengdian wang
T细胞活化诱导的细胞死亡（AICD）是一种由Fas介导的细胞凋亡，对维持免疫稳态非常重要。TOSO最早被发现是Fas介导的凋亡抑制剂，在慢性淋巴细胞白血病中过表达。最近，TOSO被鉴定为IgM FcR。在本研究中，我们制备了抗TOSO单克隆抗体（mAb），可以阻断IgM与TOSO的结合，并发现T细胞活化过程中T细胞凋亡与TOSO表达呈负相关。在体外AICD模型中，抗TOSO阻断mAb处理活化的T细胞可促进T细胞AICD，而抗TOSO阻断mAb处理异种移植物抗宿主病小鼠也可增加活化的T细胞对Fas诱导的凋亡的敏感性，并伴有c-FLIPL表达减少和AP-1复合物表达上调。总之，我们的数据表明了TOSO在T细胞AICD中的抗凋亡作用，并为血液恶性肿瘤和免疫疾病的治疗开辟了新的治疗前景。
T cell activation-induced cell death (AICD), that involves the induction of Fas-mediated apoptosis, is very important for the maintenance of immune homeostasis. TOSO was firstly described as an inhibitor of Fas-mediated apoptosis and overexpressed in chronic lymphocytic leukemia. Recently, TOSO was identified as IgM FcR. In this study, we produced anti-TOSO monoclonal antibody (mAb) that could block the binding of IgM to TOSO and found that T cell apoptosis is negatively correlated with TOSO expression during T cell activation. Treatment of activated T cells with anti-TOSO blocking mAb promoted T cell AICD in in vitro AICD model, and treatment of xenogeneic-GVHD mice with the antibody also increased the sensitivity of activated T cells to Fas-induced apoptosis, which was accompanied by reduction of c-FLIPL expression and up-regulation of AP-1 complex. In summary, our data indicate the anti-apoptotic effect of TOSO in T cell AICD and open up new therapeutic prospects for the treatment of hematologic malignancies and immune disorders.
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影响因子：
20.3
作者：
S. Brochu;B. Rioux-Massé;J. Roy;D. Roy;C. Perreault
通讯作者：
S. Brochu;B. Rioux-Massé;J. Roy;D. Roy;C. Perreault
影响因子：
20.3
作者：
C. Pallasch;A. Schulz;N. Kutsch;Janine Schwamb;S. Hagist;H. Kashkar;A. Ultsch;C. Wickenhauser
通讯作者：
C. Pallasch;A. Schulz;N. Kutsch;Janine Schwamb;S. Hagist;H. Kashkar;A. Ultsch;C. Wickenhauser
影响因子：
64.8
作者：
ANGEL, P;ALLEGRETTO, EA;KARIN, M
通讯作者：
KARIN, M
DOI：
10.1016/j.biocel.2009.02.008
发表时间：
2009-08
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Jing Zhang;Yunzi Chen;Qilai Huang;Wei Cheng;Yuan-Xi Kang;L. Shu;Wu Yin;Z. Hua
通讯作者：
Jing Zhang;Yunzi Chen;Qilai Huang;Wei Cheng;Yuan-Xi Kang;L. Shu;Wu Yin;Z. Hua
影响因子：
4.4
作者：
Schmitz, I;Weyd, H;Kirchhoff, S
通讯作者：
Kirchhoff, S