Hawke S, Stevenson P G, Freeman S, Bangham C R
Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
J Exp Med. 1998 May 18;187(10):1575-82. doi: 10.1084/jem.187.10.1575.
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.
经鼻内接种甲型流感病毒X-31的小鼠可免受随后用神经毒性甲型流感病毒WSN进行的脑内攻击，这种异型保护由CD8(+)细胞毒性T淋巴细胞介导。我们研究了这种二次免疫反应的动力学，发现尽管在第10天时复制能力强的病毒已被清除，但我们仍能够从小鼠脑内接种后至少320天的小鼠脑中回收活化的流感特异性细胞毒性T淋巴细胞（CTL），这些细胞能够杀伤新鲜离体的细胞。活化的抗病毒CTL表达高水平的早期活化标志物CD69，这表明尽管脑实质中缺乏病毒蛋白且免疫组化检测不到主要组织相容性复合体染色，并且通过单步和两步逆转录PCR检测到的病毒核酸水平几乎不可检测，但TCR信号仍在持续。活化淋巴细胞的局部持续存在对于在相对免疫特权部位易于复发的病毒进行有效的长期反应可能很重要。
