Priming of immature thymocytes to CD3-mediated apoptosis by infection with murine cytomegalovirus
Priming of immature thymocytes to CD3-mediated apoptosis by infection with murine cytomegalovirus
复制标题
鼠巨细胞病毒感染引发未成熟胸腺细胞 CD3 介导的细胞凋亡
作者：
Y. Koga;Kazuo Tanaka;Yi Lu;Masumi OH;M. Sasaki;G. Kimura;K. Nomoto
巨细胞病毒（CMV）在免疫功能低下的宿主中引起严重的临床表现;然而，尚不清楚病毒本身是否是免疫抑制的原因，或者是否作为机会性旁观者病原体参与。本研究旨在阐明CMV感染对宿主免疫系统的影响。接种亚致死剂量鼠巨细胞病毒（MCMV）的BALB/c小鼠的双阳性胸腺细胞被10微克量的抗CD 3单克隆抗体广泛耗尽，而这样的量不能诱导未感染小鼠胸腺细胞的任何明显消除。在感染宿主的未成熟胸腺细胞中，抗CD 3单克隆抗体治疗后发现对凋亡诱导的敏感性显着升高。这种双阳性胸腺细胞的信号转导通路的分析表明，抗CD 3刺激后，细胞内Ca 2+水平的深刻的升高，这意味着这种异常的动员Ca 2+信号通路中起着至关重要的作用，导致这些细胞广泛的凋亡。通过PCR检查胸腺能够在胸腺基质细胞中检测到低拷贝数的MCMV DNA，但在胸腺细胞中完全没有。因此，这表明，一种机制，这是不相关的病毒在细胞内复制发挥了关键作用，使胸腺细胞高度凋亡敏感性感染MCMV的主机。
Cytomegalovirus (CMV) causes severe clinical manifestations in immunocompromised hosts; however, it remains unclear whether the virus itself is a cause of immunosuppression or whether it is involved as an opportunistic bystander pathogen. This study was performed to elucidate the effect of CMV infection on the host's immune system. The double-positive thymocytes of BALB/c mice inoculated with a sublethal dose of murine CMV (MCMV) were extensively depleted by a 10-micrograms amount of anti-CD3 monoclonal antibody, while such an amount was unable to induce any apparent elimination of thymocytes in noninfected mice. In immature thymocytes of infected hosts, a markedly high level of susceptibility to apoptosis induction was found on treatment with anti-CD3 monoclonal antibody. Analysis of the signal transduction pathway of such double-positive thymocytes demonstrated a profound elevation of the intracellular Ca2+ level after anti-CD3 stimulation, implying that this aberrant mobilization of Ca2+ plays a crucial role in the signaling pathway leading these cells to an extensive apoptosis. Examination of the thymus by PCR was able to detect a low copy number of MCMV DNAs in thymic stromal cells but none at all in thymocytes. Therefore, it is suggested that a mechanism which is not associated with virus replication within the cells exerts a critical effect on rendering the thymocytes highly apoptosis sensitive in hosts infected with MCMV.
小鼠巨细胞病毒病对弓形虫的再激活：巨噬细胞的抗菌活性。
DOI：
10.1093/infdis/160.2.305
发表时间：
1989
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Pomeroy,C;Kline,S;Jordan,MC;Filice,GA
通讯作者：
Filice,GA