Gilden D H, Cole G A, Nathanson N
J Exp Med. 1972 Apr 1;135(4):874-89. doi: 10.1084/jem.135.4.874.
Lymphocytic choriomeningitis (LCM) virus carriers were established by intracerebral inoculation of adult BALB/c mice followed by a single dose of cyclophosphamide (CY) (150 mg/kg) 3 days after infection, and by intracerebral injection within 24 hr of birth. These carriers were then adoptively immunized with spleen cells or serum from immune or normal BALB/c donors. Transfer of immune spleen cells into drug-induced carriers consistently resulted in acutely fatal choriomeningitis, histologically strikingly similar to classical LCM. Normal spleen cells or immune serum failed to produce either central nervous system (CNS) pathology or illness with any regularity. In addition, focal necrosis of the cerebellum was seen after adoptive immunization of drug-induced carriers but only when mice received cells at least 3 wk after inoculation, which is probably explained by the gradual spread of infection from membranes to the neural parenchyma during the first month after establishment of the carrier state in adult mice. Immune spleen cells, when transferred to neonatal carriers, led to a decrease in virus titers in blood and brains and to development of antibody without acute CNS disease. It appears that the production of fatal choriomeningitis after LCM infection is determined in part by the distribution of viral antigen, and this is markedly different in neonatal and drug-induced carriers at the time of cell transfer. Another factor of potential importance is the much higher level of circulating viral antigen in the plasma of neonatal than in that of drug-induced LCM carriers. Classical LCM disease can only be transferred by immune lymphoid cells and not by antiserum. Furthermore, little or no complement-fixing (CF) antibody was found in the plasma of mice dying of acute choroiditis. These observations strongly suggest that acute choroiditis is dependent upon the cell-mediated immune response.
通过在成年BALB/c小鼠脑内接种淋巴细胞性脉络丛脑膜炎（LCM）病毒，然后在感染后3天给予单剂量环磷酰胺（CY）（150mg/kg），以及在出生后24小时内进行脑内注射，建立了LCM病毒携带者。然后用来自免疫或正常BALB/c供体的脾细胞或血清对这些携带者进行过继免疫。将免疫脾细胞转移到药物诱导的携带者中始终导致急性致命性脉络丛脑膜炎，组织学上与经典LCM极为相似。正常脾细胞或免疫血清未能规律性地产生中枢神经系统（CNS）病变或疾病。此外，在对药物诱导的携带者进行过继免疫后可见小脑局灶性坏死，但仅当小鼠在接种后至少3周接受细胞时才会出现，这可能是由于在成年小鼠建立携带者状态后的第一个月内感染从脑膜逐渐扩散到神经实质所致。当将免疫脾细胞转移到新生携带者中时，会导致血液和脑中病毒滴度降低以及抗体产生，且无急性CNS疾病。看来LCM感染后致命性脉络丛脑膜炎的产生部分取决于病毒抗原的分布，而在细胞转移时新生和药物诱导的携带者中的这种分布明显不同。另一个潜在重要因素是新生小鼠血浆中循环病毒抗原水平比药物诱导的LCM携带者血浆中的水平高得多。经典LCM疾病只能通过免疫淋巴细胞而不能通过抗血清进行转移。此外，在死于急性脉络膜炎的小鼠血浆中几乎未发现或未发现补体结合（CF）抗体。这些观察结果强烈表明急性脉络膜炎依赖于细胞介导的免疫反应。
