Erälinna J P, Soilu-Hänninen M, Röyttä M, Ilonen J, Mäkelä A, Salonen R
Department of Virology, University of Turku, Finland.
J Neuroimmunol. 1994 Nov;55(1):81-90. doi: 10.1016/0165-5728(94)90149-x.
Infection with an avirulent strain of Semliki Forest virus (SFV-A7) facilitates the development of experimental allergic encephalomyelitis (EAE) in a genetically resistant BALB/c mouse strain. Irradiation which is necessary for EAE induction caused a decrease in the total number of lymphocytes and an increase in CD4+/CD8+ T cell ratio in the spleen of BALB/c mice. EAE induction increased the ratio further until clinical and histological signs of EAE appeared. Entry of perivascular CD4+ and CD8+ cells preceded the onset of clinical signs and the appearance of MAC-1+ cells in the central nervous system (CNS). In the acute phase of EAE, cellular infiltrates, which were sparse, consisted mainly of MAC-1+ cells and a few CD4+ and CD8+ cells. Inflammatory cells gradually disappeared during the recovery phase. SFV-A7 infection after irradiation and EAE induction did not significantly change the CD4+/CD8+ ratio in the spleen or in the CNS infiltrates but enhanced the entry of inflammatory cell into the CNS. Similar perivascular cell influx was also seen in untreated mice infected with SFV-A7. We conclude that observed rapid reduction of splenic mononuclear cells and increase of the CD4+/CD8+ T cell ratio caused by irradiation prior EAE induction are early crucial events in disease induction in this resistant strain of mice. SFV-A7 infection, which further facilitates the development of EAE, does not induce immunoregulatory changes but provides its effect by enhancing the entry of inflammatory cells into the CNS. The combination of these two mechanisms thus effectively breaks the natural resistance against EAE in this genetically resistant mouse strain.
用减毒的塞姆利基森林病毒（SFV - A7）感染，可促使基因抗性的BALB/c小鼠品系发生实验性自身免疫性脑脊髓炎（EAE）。诱导EAE所需的照射导致BALB/c小鼠脾脏中淋巴细胞总数减少，CD4⁺/CD8⁺ T细胞比例增加。EAE诱导进一步提高了该比例，直至出现EAE的临床和组织学症状。血管周围CD4⁺和CD8⁺细胞的进入先于临床症状的出现以及中枢神经系统（CNS）中MAC - 1⁺细胞的出现。在EAE急性期，稀疏的细胞浸润主要由MAC - 1⁺细胞以及少数CD4⁺和CD8⁺细胞组成。在恢复阶段，炎性细胞逐渐消失。照射和EAE诱导后进行SFV - A7感染，并未显著改变脾脏或CNS浸润中的CD4⁺/CD8⁺比例，但增强了炎性细胞进入CNS。在感染SFV - A7的未处理小鼠中也观察到类似的血管周围细胞流入。我们得出结论，在EAE诱导前照射导致的脾脏单核细胞快速减少以及CD4⁺/CD8⁺ T细胞比例增加，是这种抗性小鼠品系疾病诱导过程中的早期关键事件。进一步促进EAE发展的SFV - A7感染，并未诱导免疫调节变化，而是通过增强炎性细胞进入CNS发挥作用。因此，这两种机制的结合有效地打破了这种基因抗性小鼠品系对EAE的天然抗性。
