Pfau C J, Valenti J K, Pevear D C, Hunt K D
J Exp Med. 1982 Jul 1;156(1):79-89. doi: 10.1084/jem.156.1.79.
Two types of lymphocytic choriomeningitis (LCM) viruses were studied which, upon intracerebral injection into adult C3H mice, provoked either (a) acute fatal central nervous system (CNS) disease or (b) life-long persistent infection. Both virus types, (a) aggressive and (b) docile, had been found to induce LCM-specific lymphocytes with comparable in vitro lytic activity (11). Because the requirement for T cells in the development of adult LCM disease has been extensively documented, we sought other reasons for the lack of acute disease in mice infected with docile virus. A striking correlation was found between the outcome of the infection and spread of virus to visceral organs. Adoptive transfer experiments showed that a 300-plaque forming unit inoculum of docile virus induced a population of T cells in donor mice fully capable of causing CNS disease in identically infected recipients. This disease causing ability was lost if the interaction was delayed beyond 3 d after infection of the recipients, but could be preserved by lowering the size of the viral inoculum in the recipients. Furthermore, without adoptive transfer, very low intracerebral doses of docile virus (which mimicked the normally slow spread of aggressive virus) were lethal. On the other hand, very high doses of aggressive virus, which mimicked the normally rapid spread of docile virus, did not induce fatal CNS disease. The results suggest that rapid dissemination of the LCM infection creates multiple target organs which divert the focused lethal T cell attack on the brain.
对两种淋巴细胞性脉络丛脑膜炎（LCM）病毒进行了研究，将它们脑内注射到成年C3H小鼠后，要么引发（a）急性致命性中枢神经系统（CNS）疾病，要么引发（b）终身持续性感染。已发现这两种病毒类型，即（a）侵袭性的和（b）温和性的，均可诱导出具有相当体外裂解活性的LCM特异性淋巴细胞（11）。由于成年LCM疾病发展过程中对T细胞的需求已得到广泛记录，我们寻找了感染温和性病毒的小鼠未患急性疾病的其他原因。发现感染结果与病毒向内脏器官的传播之间存在显著相关性。过继转移实验表明，300个噬斑形成单位接种量的温和性病毒在供体小鼠中诱导出一群T细胞，这些T细胞完全有能力在相同感染的受体小鼠中引发CNS疾病。如果在受体小鼠感染后3天以上延迟这种相互作用，这种致病能力就会丧失，但可以通过降低受体小鼠中病毒接种量来保留。此外，在没有过继转移的情况下，极低脑内剂量的温和性病毒（模拟侵袭性病毒通常缓慢的传播）具有致死性。另一方面，极高剂量的侵袭性病毒，模拟温和性病毒通常快速的传播，并未诱发致命的CNS疾病。结果表明，LCM感染的快速传播会产生多个靶器官，从而转移了聚焦于大脑的致命T细胞攻击。
