Renno T, Taupin V, Bourbonnière L, Verge G, Tran E, De Simone R, Krakowski M, Rodriguez M, Peterson A, Owens T
Neuroimmunology Unit, Montreal Neurological Institute, 3801 University, Montreal, Quebec, H3A 2B4, Canada.
Mol Cell Neurosci. 1998 Dec;12(6):376-89. doi: 10.1006/mcne.1998.0725.
The cytokine interferon-gamma (IFNgamma) is implicated in the induction of acute CNS inflammation, but it is less clear what role if any IFNgamma plays in progression to chronic demyelination and neurological deficit. To address this issue, we have expressed IFNgamma in myelinating oligodendrocytes of transgenic mice. MHC I immunostaining and iNOS mRNA were upregulated in their CNS, but such transgenic mice showed no spontaneous CNS inflammation or demyelination, and the incidence, severity, and histopathology of experimental autoimmune encephalomyelitis (EAE) were similar to nontransgenic controls. In contrast to control mice, which remit from EAE with resolution of glial reactivity and leukocytic infiltration, transgenics showed chronic neurological deficits. While activated microglia/macrophages persisted in demyelinating lesions for over 100 days, CD4(+) T lymphocytes were no longer present in CNS. IFNgamma therefore may play a role in chronic demyelination and long-term disability following the induction of demyelinating disease. Because IFNgamma may have neural as well as immune-infiltrating origins, these findings generate a new perspective on its role in the CNS.
细胞因子γ干扰素（IFNγ）与急性中枢神经系统炎症的诱导有关，但尚不清楚IFNγ在进展为慢性脱髓鞘和神经功能缺损中是否发挥作用（若有作用，其作用是什么）。为解决这一问题，我们在转基因小鼠的髓鞘形成少突胶质细胞中表达了IFNγ。其中枢神经系统中MHC I免疫染色和iNOS mRNA上调，但此类转基因小鼠未出现自发性中枢神经系统炎症或脱髓鞘，且实验性自身免疫性脑脊髓炎（EAE）的发病率、严重程度和组织病理学与非转基因对照相似。与随着胶质细胞反应性和白细胞浸润消退而从EAE中恢复的对照小鼠不同，转基因小鼠表现出慢性神经功能缺损。虽然活化的小胶质细胞/巨噬细胞在脱髓鞘病变中持续存在超过100天，但中枢神经系统中不再存在CD4(+) T淋巴细胞。因此，IFNγ可能在脱髓鞘疾病诱导后的慢性脱髓鞘和长期残疾中发挥作用。由于IFNγ可能来源于神经以及免疫浸润细胞，这些发现为其在中枢神经系统中的作用带来了新的视角。
