Myelin oligodendrocyte glycoprotein peptide-induced experimental allergic encephalomyelitis and T cell responses are unaffected by immunoproteasome deficiency

Myelin oligodendrocyte glycoprotein peptide-induced experimental allergic encephalomyelitis and T cell responses are unaffected by immunoproteasome deficiency
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DOI:
10.1016/j.jneuroim.2007.09.024
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发表时间:
2007-12-01
影响因子:
3.3
通讯作者:
Whitton, J. Lindsay
Whitton, J. Lindsay
中科院分区:
医学4区
文献类型:
--
作者:
Frausto, Ricardo F.;Crocker, Stephen J.;Whitton, J. Lindsay

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将MOG肽接种到C57 BL/6小鼠中诱导CD 4(+)和CD 8(+)T细胞,并且最近的工作已经表明,在广泛的体外刺激后,后一群体的过继转移可以在幼稚受体小鼠中引起EAE。在此,我们评估了EAE的发生率和严重程度。以及在野生型小鼠和缺乏完整免疫蛋白酶体的LMP-2KO小鼠的MOG肽接种后诱导CD 4+和CD 8 + T细胞,所述完整免疫蛋白酶体是由慢性炎症诱导的细胞质细胞器,并且对于将MHC I类表位呈递给CD 8(被分割)T细胞可能是重要的。我们报道了通过临床和组织学标准评估的EAE在LMP-2KO小鼠和野生型C57 B/6小鼠(wt)中对MOG肽MOG(35-55)和MOG(40-54)免疫的响应是相似的,这表明免疫蛋白酶体在脱髓鞘疾病的发展中不起关键作用。此外,与先前的报道一致,肽特异性CD 8 + T细胞在肽免疫小鼠的CNS中几乎检测不到,尽管肽特异性CD 4 + T细胞是丰富的。因此,我们使用了一种新的技术来寻找自身反应性的CD 8 + T细胞在MOG肽免疫的小鼠,我们报告的鉴定CD 4+和CD 8 + T细胞,晚至19天后肽注射,积极生产IFN-γ在体内,在体内抗原接触的反应。(c)2007 Elsevier B.V保留所有权利。
The inoculation of MOG peptides into C57BL/6 mice induces CD4(+) and CD8(+) T cells, and recent work has shown that adoptive transfer of the latter population, after extensive in vitro stimulation, can cause EAE in naive recipient mice. Herein, we have evaluated the incidence and severity of EAE. and the induction of CD4+ and CD8+ T cells, following MOG peptide inoculation of wt mice and of LMP-2KO mice that lack an intact immunoproteasome, a cytoplasmic organelle that is induced by chronic inflammation and that may be important for the presentation of MHC class I epitopes to CD8(divided by) T cells. We report that EAE, evaluated by both clinical and histological criteria, is similar in LMP-2KO mice and wildtype C57B/6 mice (wt) in response to immunization with MOG peptides MOG(35-55) and MOG(40-54), suggesting that the immunoproteasome does not play a key role in the development of demyelinating disease. Furthermore, and consistent with previous reports, peptide-specific CD8+ T cells were barely detectable in the CNS of peptide-immunized mice, although peptide-specific CD4+ T cells were abundant. Therefore, we used a new technique to look for autoreactive CD8+ T cells in MOG peptide-immunized mice, and we report the identification of CD4+ and CD8+ T cells that, as late as 19 days after peptide injection, are actively producing IFN-gamma in vivo, in response to in vivo antigen contact. (c) 2007 Elsevier B.V All rights reserved.