Interferon-gamma confers resistance to experimental allergic encephalomyelitis
Interferon-gamma confers resistance to experimental allergic encephalomyelitis
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DOI：
10.1002/eji.1830260735
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发表时间：
1996-07-01
影响因子：
5.4
通讯作者：
Owens, T
中科院分区：
文献类型：
--
作者：
Krakowski, M;Owens, T
在实验性变态反应性脑脊髓炎(EAE)中，T细胞渗入中枢神经系统(CNS)并诱导炎症。这些CD4(+)T细胞分泌干扰素-γ，其水平与疾病的严重程度相关，并被认为在疾病诱导中发挥关键作用。许多品系的小鼠对EAE具有抵抗力。我们研究了干扰素-γ缺失对耐药BALB/c回交小鼠诱发EAE能力的影响。不出所料，BALB/c或BALB/c回交小鼠在免疫佐剂中加入髓鞘碱性蛋白后，仅有0-6%的小鼠发生了EAE。引人注目的是，通过靶向干扰干扰素-伽马基因(GKO小鼠)来消除干扰素-伽马的表达，将它们转变为易感表型。在这些缺乏干扰素的小鼠中，多达71%的小鼠患上了EAE，这一频率与敏感的SJL/J株相当。此外，在缺乏干扰素-γ的小鼠中，EAE的严重程度异常高。干扰素-γ缺陷小鼠的疾病免疫学特征与易感(SJL/J)的EAE小鼠相似，包括中枢血管周围的渗透和脊髓中CD3-伽马链和肿瘤坏死因子-αmRNA水平的数量级增加。因此，我们证明，缺乏干扰素-γ可以转化为抗EAE的小鼠品系，使其变得对疾病敏感。因此，在BALB/c小鼠中，干扰素-γ对EAE具有抵抗力。
In experimental allergic encephalomyelitis (EAE), T cells infiltrate the central nervous system (CNS) and induce inflammation. These CD4(+) T cells secrete interferon (IFN)-gamma, levels of which correlate with disease severity, and which is proposed to play a key role in disease induction. Many strains of mice are resistant to EAE. We have studied the effect of deletion of IFN-gamma on the ability to induce EAE in resistant BALB/c-backcrossed mice. As expected, only 0-6 % of BALB/c or BALB/c-backcrossed mice developed EAE when immunized with myelin basic protein in adjuvant. Strikingly, abrogation of IFN-gamma expression by targeted disruption of the IFN-gamma gene (GKO mice) converted them to a susceptible phenotype. As many as 71 % of these IFN-gamma-deficient mice developed EAE, a frequency comparable to that seen with the susceptible SJL/J strain. In addition, EAE was of unusually high severity in mice lacking IFN-gamma. Immunological characteristics of disease in IFN-gamma-deficient mice were comparable to those seen in susceptible (SJL/J) mice with EAE, including perivascular infiltration in the CNS and order-of-magnitude increases for both CD3 gamma chain and TNF-alpha mRNA levels in the spinal cord. We thus demonstrate that lack of IFN-gamma converts an otherwise EAE-resistant mouse strain to become susceptible to disease. Therefore, in BALB/c mice, IFN-gamma confers resistance to EAE.