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首页> 外文期刊>Journal of Chinese Pharmaceutical Sciences >Anti-CD132 Monoclonal Antibodies Inducing T Cells Apoptosis after Alloantigen Stimulation and Its Possible Clinical Applications
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Anti-CD132 Monoclonal Antibodies Inducing T Cells Apoptosis after Alloantigen Stimulation and Its Possible Clinical Applications

机译:抗CD132单克隆抗体诱导同种抗原刺激后T细胞凋亡及其可能的临床应用

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Aim To investigate the mechanism of anti-CD132 monoclonal antibodies (mAbs) inhibiting T cells proliferation in vitro, and their potential values for clinical use. Methods BALB/c and C57BL/6 mice splenocytes were harvested for two-ways mixed lymphocyte culture (MLC). Anti-CD132 mAbs (final concentration 100 mg·L~(-1)) were added in MLC on day 0 (group 1) or day 3 (group 2). Fluorescence activated cell sorting (FACS) was used to measure the proliferation (carboxy-fluorescein dia cetate, succinimidyl ester, CFSE), apoptosis of T cells (PE-CD3, FTTC-annexin-v), and cell cycle (pro-pidium iodide stain) . The expression of survivin in T cells was detected by immunochemical stai-ning. Re-sults Multi-generation CFSE-labeled splenocytes were found dividing and their fluorescent strength decreased in MLC. There was no noticeable change in fluorescent intensity in group 1 and group 2. On day 3, apoptosis induced by anti-CD132 mAbs was detected in part of T cells, but was not detected in the former two days in group 1. In group 2, the number of cells in M phase (activated T cells) decreased and apoptot-ic cells increased on day 4. The phenomena were not observed in control group (P < 0.01). Expression of survivin in T cells was detected in control group but not in groups 1 and 2. Conclusion Blockade of CD132 signaling pathway inhibits T cell proliferation in vitro by means of inducing activated alloreactive T cell apoptosis but not the resting T cells. Anti-CD132 mAbs may be candidates for clinical applications.
机译:目的探讨抗CD132单克隆抗体(mAbs)体外抑制T细胞增殖的机制,及其在临床上的潜在价值。方法收集BALB / c和C57BL / 6小鼠脾细胞进行双向混合淋巴细胞培养(MLC)。在第0天(第1组)或第3天(第2组)将抗CD132 mAb(终浓度为100 mg·L〜(-1))添加到MLC中。荧光激活细胞分选术(FACS)用于测量增殖(醋酸丁二酯,琥珀酰亚胺酯,CFSE),T细胞的凋亡(PE-CD3,FTTC-annexin-v)和细胞周期(碘化丙锭)污点)。免疫化学法检测survivin在T细胞中的表达。结果发现多代CFSE标记的脾细胞分裂,MLC中的荧光强度降低。第1组和第2组的荧光强度没有明显变化。在第3天,在第1组的前两天,在部分T细胞中检测到了由抗CD132 mAb诱导的凋亡,而在第1组中,没有检测到。在第4天,M期细胞(活化的T细胞)减少,凋亡细胞增加。在对照组中未观察到该现象(P <0.01)。对照组中未检测到生存素在T细胞中的表达,而在第1组和第2组中则检测到。结论CD132信号通路的阻断在体外通过诱导活化的同种反应性T细胞凋亡而在静息T细胞中抑制了T细胞增殖。抗CD132 mAb可能是临床应用的候选药物。

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