The relationship of nyasthenia gravis and apoptosis in human thymus : the anallysis of CAD, DNase and AIF

重症肌无力与人胸腺细胞凋亡的关系：CAD、DNase、AIF分析

• 批准号: 12671322
• 负责人: KIRIYAMA Masanobu
• 金额: $ 1.98万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671322/
• 关键词: caspase; AIF; Negative selection; apoptosis; mitochondria; caspase; 重症筋無力症; 胸腺; CAD; DNaseγ; アポトーシス; Dexamethasone; Etoposide

Negative selection is a mechanism through which developing thymocytes expressing a TCR with high affinity for self peptide-MHC complexes are eliminated by apoptosis. Isolated human thymocytes were induced to undergo apoptosis by combined use of antii-CD3 and CD28 mAbs. The activation of caspase-3 was detected in thymocytes cultured in the presence of antibodies. Although the activation of caspase-3 was blocked by the caspase inhibitor zVAD.fmk, cell death still occurred with only partial condensation of chromatin and without internucleosomal DNA fragmentation, maintaining other features of apoptosis, such as Δ Ψ_m collapse. We detected expression of AIF in human thymocytes undergoing apoptosis induced by antibodies to CD3 and CD28 in the presence or absence of zVAD.fmk. In the in vitro negative selection model of humam thymocytes, apoptosis can proceed in caspase-dependent and caspase-independent pathways. AIF may be responsible for the latter pathway.

负选择是一种机制，通过该机制，表达对自身肽-MHC复合物具有高亲和力的TCR的发育中的胸腺细胞被凋亡消除。分离的人胸腺细胞通过联合使用抗i-CD 3和CD 28单克隆抗体进行诱导凋亡。在抗体存在下培养的胸腺细胞中检测到caspase-3的活化。虽然caspase-3的激活被caspase抑制剂zVAD. ffnu阻断，但细胞死亡仍然发生，只有部分染色质浓缩，没有核小体间DNA片段化，保持了凋亡的其他特征，如Δ_m塌陷。我们检测了在存在或不存在zVAD. fmk的情况下经历由CD 3和CD 28抗体诱导的凋亡的人胸腺细胞中AIF的表达。在人胸腺细胞的体外负选择模型中，凋亡可以通过caspase依赖和caspase非依赖途径进行。AIF可能负责后一种途径。