Macrophage infiltration, but not apoptosis, is correlated with immune-mediated demyelination following murine infection with a neurotropic coronavirus
Macrophage infiltration, but not apoptosis, is correlated with immune-mediated demyelination following murine infection with a neurotropic coronavirus
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DOI：
10.1128/jvi.73.10.8771-8780.1999
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发表时间：
1999-10-01
影响因子：
5.4
通讯作者：
Perlman, S
中科院分区：
文献类型：
--
作者：
Wu, GF;Perlman, S
感染小鼠肝炎病毒 JHM 株 (MHV-JHM) 的小鼠会患上慢性脱髓鞘性脑脊髓炎，这在很大程度上是免疫介导的。使用过继转移系统评估免疫活性的潜在机制。重组酶激活基因功能缺陷（RAG1(-/-)）、B 细胞和 T 细胞成熟缺陷的小鼠会持续感染 MHV，但不会发生脱髓鞘。将免疫 MHV 的小鼠的脾细胞过继转移到感染了减毒病毒株的 RAG1(-/-) 小鼠中，导致脱髓鞘的快速、渐进性发展。最引人注目的是，过继转移在 5 至 6 天内导致活化的巨噬细胞/小胶质细胞广泛募集到脊髓内的脱髓鞘部位。病毒抗原的清除优先发生在脊髓灰质中。在过继移植前后，RAG1(-/-)小鼠的中枢神经系统(CNS)灰质和白质中均发现了凋亡细胞，脱髓鞘发生后，凋亡细胞数量适度增加，但分布不增加。这些结果表明，MHV-JHM 感染小鼠中枢神经系统后的细胞凋亡不足以引起脱髓鞘。这些结果表明，RAG(-/-) 小鼠免疫重建后巨噬细胞募集和髓磷脂破坏迅速发生，表明这将是研究 MHV 诱导的脱髓鞘的有用系统。
Mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis that is in large part immune mediated. Potential mechanisms of immune activity were assessed using an adoptive transfer system. Mice deficient in recombinase-activating gene function (RAG1(-/-)), defective in B- and T-cell maturation, become persistently infected with MHV but do not develop demyelination. Adoptive transfer of splenocytes from mice immunized to MHV into RAG1(-/-) mice infected with an attenuated strain of the virus results in the rapid and progressive development of demyelination. Most striking, adoptive transfer resulted, within 5 to 6 days, in extensive recruitment of activated macrophages/microglia to sites of demyelination within the spinal cord. Clearance of virus antigen occurred preferentially from the gray matter of the spinal cord. Apoptotic cells were identified in both the gray and white matter of the central nervous system (CNS) from RAG1(-/-) mice before and after adoptive transfer, with a moderate increase in number, but not distribution, of apoptotic cells following the development of demyelination. These results suggest that apoptosis following MHV-JHM infection of the murine CNS is not sufficient to cause demyelination. These results, showing that macrophage recruitment and myelin destruction occur rapidly after immune reconstitution of RAG(-/-) mice, suggest that this will be a useful system for investigating MHV-induced demyelination.