Long-term persistence of activated cytotoxic T lymphocytes after viral infection of the central nervous system
Long-term persistence of activated cytotoxic T lymphocytes after viral infection of the central nervous system
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DOI：
10.1084/jem.187.10.1575
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发表时间：
1998-05-18
影响因子：
15.3
通讯作者：
Bangham, CRM
中科院分区：
文献类型：
--
作者：
Hawke, S;Stevenson, PG;Bangham, CRM
鼻内接种流感A/X-31的小鼠可保护其免受随后的神经毒性流感A/WSN脑内攻击，这种异型保护由CD 8（+）细胞毒性T淋巴细胞介导。我们已经研究了这种二次免疫应答的动力学，发现尽管在第10天消除了具有复制能力的病毒，但我们能够在脑内接种后至少320天从小鼠脑中回收新鲜体外杀死的活化流感特异性细胞毒性T淋巴细胞（CTL）。激活的抗病毒CTLs表达高水平的早期激活标记物CD 69，这表明尽管脑实质中缺乏病毒蛋白和主要组织相容性复合体免疫组织化学染色，并且通过一步和两步逆转录PCR几乎检测不到病毒核酸水平，但TCR信号仍在继续。活化淋巴细胞的局部持久性对于在相对免疫豁免的部位对易于复发的病毒的有效长期应答可能是重要的。
Mice intranasally inoculated with influenza A/X-31 are protected against a subsequent intracerebral challenge with the neurovirulent influenza A/WSN and this heterotypic protection is mediated by CD8(+) cytotoxic T lymphocytes. We have studied the kinetics of this secondary immune response and found that despite the elimination of replication-competent virus by day 10, we were able to recover activated influenza-specific cytotoxic T lymphocytes (CTLs) that killed freshly ex vivo from the brains of mice for at least 320 d after the intracerebral inoculation. The activated antiviral CTLs expressed high levels of the early activation marker CD69, suggesting continuing TCR signaling despite a lack of viral protein and major histocompatibility complex staining by immunohistochemistry in the brain parenchyma and barely detectable levels of viral nucleic acid by single and two-step reverse transcription PCR. Local persistence of activated lymphocytes may be important for efficient long-term responses to viruses prone to recrudesce in sites of relative immune privilege.