T-cell properties determine disease site, clinical presentation, and cellular pathology of experimental autoimmune encephalomyelitis
T-cell properties determine disease site, clinical presentation, and cellular pathology of experimental autoimmune encephalomyelitis
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DOI：
10.1016/s0002-9440(10)63410-4
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发表时间：
2004-11-01
影响因子：
6
通讯作者：
Dorf, M
中科院分区：
文献类型：
--
作者：
Abromson-Leeman, S;Bronson, R;Dorf, M
在用髓鞘碱性蛋白致脑炎肽免疫的BALB干扰素-γ基因敲除小鼠中观察到两种不同的实验性自身免疫性脑脊髓炎临床表型。以上行无力和麻痹为特征的常规疾病在用包含残基59至76的肽免疫后以更高的频率发生。轴向旋转疾病，其特征在于不受控制的轴向旋转，发生在用对应于全长21.5 kd蛋白的外显子2的肽免疫的小鼠中的频率更高。两种临床表型在组织学上是可区分的。p常规疾病的特征在于主要在脊髓中的炎症和脱髓鞘，而轴向旋转疾病涉及脑的外侧髓区的炎症和脱髓鞘。两种类型都有以中性粒细胞为主的浸润。通过分离T细胞并将疾病转移给幼稚受体，我们在这里表明疾病的类型完全由诱导T细胞决定。此外，使用CXCR 2敲除受体的研究表明，尽管中性粒细胞对于这些T细胞中的一些细胞影响疾病是至关重要的，但也有干扰素-γ缺陷的T细胞在干扰素-γ和中性粒细胞都不存在的情况下诱导疾病。这些结果突出了炎症和脱髓鞘可用的T细胞启动的效应子途径的多样性。
Two distinct clinical phenotypes of experimental autoimmune encephalomyelitis are observed in BALB interferon-gamma knockout mice immunized with encephalitogenic peptides of myelin basic protein. Conventional disease, characterized by ascending weakness and paralysis, occurs with greater frequency after immunizing with a peptide comprising residues 59 to 76. Axial-rotatory disease, characterized by uncontrolled axial rotation, occurs with greater frequency in mice immunized with a peptide corresponding to exon 2 of the full length 21.5-kd protein. The two clinical phenotypes are histologically distinguishable.. p Conventional disease is characterized by inflammation and demyelination primarily in spinal cord, whereas axial-rotatory disease involves inflammation and demyelination of lateral medullary areas of brain.. pes have infiltrates in which neutrophils are a Both types have infiltrates in which neutrophils are a predominating component. By isolating T cells and transferring disease to naive recipients, we show here that the type of disease is determined entirely by the inducing T cell. Furthermore, studies using CXCR2 knockout recipients, unable to recruit neutrophils to inflammatory sites, show that although neutrophils are critical for some of these T cells to effect disease, there are also interferon-gamma-deficient T cells that induce disease in the absence of both interferon-gamma and neutrophils. These results highlight the multiplicity of T-cell-initiated effector pathways available for inflammation and demyelination.