A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy.
A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy.
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DOI：
10.1084/jem.20082113
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发表时间：
2009-03-16
期刊：
影响因子：
--
通讯作者：
Bluestone JA
中科院分区：
文献类型：
--
作者：
Louvet C;Kabre BG;Davini DW;Martinier N;Su MA;DeVoss JJ;Rosenthal WL;Anderson MS;Bour-Jordan H;Bluestone JA
B7-2缺陷的自身免疫易感性非肥胖糖尿病小鼠自发地发展由炎性CD 4 + T细胞介导的自身免疫性周围神经病变，其使人联想到格林-巴利综合征和慢性炎性脱髓鞘性多发性神经病。为了确定这种疾病的病因，从发炎组织来源的CD 4 + T细胞产生CD 4 + T细胞杂交瘤。大多数T细胞杂交瘤对髓磷脂蛋白0（P0）具有特异性，髓磷脂蛋白0是靶向神经蛋白的自身抗体应答的主要靶标。为了确定P0特异性T细胞反应是否足以介导疾病，我们产生了一种新的髓鞘P0特异性T细胞受体转基因（POT）小鼠。POT T细胞在胸腺发育过程中不耐受或缺失，并在体外响应于P0而增殖。重要的是，当在重组激活基因敲除背景下繁殖时，POT小鼠发展成暴发性形式的周围神经病变，其影响到断奶年龄的所有小鼠，并导致它们在3-5周龄时过早死亡。这种突发性疾病与P0特异性T细胞产生干扰素γ和缺乏CD 4 + Foxp 3+调节性T细胞有关。总的来说，我们的数据表明，髓磷脂P0是一个主要的自身抗原在自身免疫性周围神经病变。
Autoimmune-prone nonobese diabetic mice deficient for B7-2 spontaneously develop an autoimmune peripheral neuropathy mediated by inflammatory CD4+ T cells that is reminiscent of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. To determine the etiology of this disease, CD4+ T cell hybridomas were generated from inflamed tissue–derived CD4+ T cells. A majority of T cell hybridomas were specific for myelin protein 0 (P0), which was the principal target of autoantibody responses targeting nerve proteins. To determine whether P0-specific T cell responses were sufficient to mediate disease, we generated a novel myelin P0–specific T cell receptor transgenic (POT) mouse. POT T cells were not tolerized or deleted during thymic development and proliferated in response to P0 in vitro. Importantly, when bred onto a recombination activating gene knockout background, POT mice developed a fulminant form of peripheral neuropathy that affected all mice by weaning age and led to their premature death by 3–5 wk of age. This abrupt disease was associated with the production of interferon γ by P0-specific T cells and a lack of CD4+ Foxp3+ regulatory T cells. Collectively, our data suggest that myelin P0 is a major autoantigen in autoimmune peripheral neuropathy.
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影响因子：
4.4
作者：
KHALILISHIRAZI, A;HUGHES, RAC;GREGSON, N
通讯作者：
GREGSON, N
影响因子：
3.3
作者：
KHALILISHIRAZI, A;ATKINSON, P;HUGHES, RAC
通讯作者：
HUGHES, RAC
影响因子：
64.8
作者：
TISCH, R;YANG, XD;MCDEVITT, HO
通讯作者：
MCDEVITT, HO
DOI：
10.4049/jimmunol.181.12.8753
发表时间：
2008-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kim HJ;Jung CG;Jensen MA;Dukala D;Soliven B
通讯作者：
Soliven B
DOI：
10.1111/j.1085-9489.2005.0010207.x
发表时间：
2005-06-01
影响因子：
3.8
作者：
Allen, D;Giannopoulos, K;Hughes, RAC
通讯作者：
Hughes, RAC