Peripheral blood CD8αα+CD11c+MHC-II+CD3- cells attenuate autoimmune glomerulonephritis in rats.
Peripheral blood CD8αα+CD11c+MHC-II+CD3- cells attenuate autoimmune glomerulonephritis in rats.
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外周血CD8αα+CD11C+MHC-II+CD3-细胞减弱大鼠的自身免疫性肾小球肾炎。
DOI：
10.1038/ki.2013.456
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发表时间：
2014-05
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
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作者：
在抗GBM肾小球肾炎（GN）模型中，GN抗性刘易斯大鼠自然地从早期肾小球炎症恢复。在这里，我们研究了恢复机制，以开发一种潜在的自身免疫性GN免疫疗法。我们以前的研究表明，具有CD 8 αα+ CD 11 c +MHC−II+ CD 3 −表型的肾小球浸润性白细胞（GIL CD 8 αα+细胞）通过诱导T细胞凋亡负责恢复。现在，我们鉴定了外周血CD 8 αα+ CD 11 c +MHC−II+ CD 3 −细胞（PBMC CD 8 αα+ CD 3 −细胞），其与GIL CD 8 αα+细胞共有9个标记。孵育后，PBMC CD 8 αα+ CD 3 −细胞显示出类似树突状细胞的形态。与GIL CD 8 αα+细胞类似，PBMC CD 8 αα+ CD 3 −细胞能够在体外诱导T细胞凋亡。因此，PBMC CD 8 αα+ CD 3 −细胞可能是GIL CD 8 αα+细胞的前体。我们接下来测试了它们的潜在体内功能。PBMC CD 8 αα+ CD 3 −细胞能够浸润炎症肾小球，但不能浸润正常肾小球。将刘易斯大鼠的分离PBMC CD 8 αα+ CD 3 −细胞转移至处于早期炎症阶段（第17-25天）的GN易感Wistar京都大鼠中。当在第45天检查时，组织病理学和BUN/血清肌酐水平均显示80%的细胞受体Wistar京都大鼠的GN显著减弱。单独的实验证实了转移的刘易斯PBMC CD 8 αα+ CD 3 −浸润到受体Wistar京都大鼠的肾小球中，并伴有凋亡的CD 4 + T细胞。因此，刘易斯大鼠的PBMC CD 8 αα+ CD 3 −细胞能够终止肾小球中正在进行的自身免疫性炎症。
In an anti-GBM glomerulonephritis (GN) model, GN-resistant Lewis rats naturally recover from early glomerular inflammation. Here we investigated recovery mechanisms for development of a potential immunotherapy for autoimmune GN. Our previous studies suggested that glomeruli-infiltrating leukocytes with a phenotype of CD8αα+CD11c+MHC−II+CD3− (GIL CD8αα+ cells) were responsible for recovery through induction of T cell apoptosis. Now, we identified peripheral blood CD8αα+CD11c+MHC−II+CD3− cells (PBMC CD8αα+CD3− cells), which shared 9 markers with GIL CD8αα+ cells. Upon incubation, PBMC CD8αα+CD3− cells displayed a morphology resembling that of dendritic cells. Similar to GIL CD8αα+ cells, PBMC CD8αα+CD3− cells were capable of inducing T cell apoptosis in vitro. Hence, PBMC CD8αα+CD3− cells were likely the precursor of GIL CD8αα+ cells. We next tested their potential in vivo function. PBMC CD8αα+CD3− cells were able to infiltrate inflamed but not normal glomeruli. Isolated PBMC CD8αα+CD3− cells of Lewis rats were transferred into GN-prone Wistar Kyoto rats at early inflammatory stage (day 17–25). When examined at day 45, both histopathology and BUN/serum creatinine level showed significantly attenuated GN in 80% of cell recipient Wistar Kyoto rats. Separate experiments verified infiltration of transferred Lewis PBMC CD8αα+CD3− into the glomeruli, accompanied with apoptotic CD4+ T cells in the glomeruli of the recipient Wistar Kyoto rats. Thus, PBMC CD8αα+CD3− cells of Lewis rats were able to terminate ongoing autoimmune inflammation in the glomeruli.
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影响因子：
56.9
作者：
Morgan, Richard A.;Dudley, Mark E.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
2.8
作者：
O'Brien K;Gran B;Rostami A
通讯作者：
Rostami A
DOI：
10.1084/jem.20092618
发表时间：
2010-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Poulin LF;Salio M;Griessinger E;Anjos-Afonso F;Craciun L;Chen JL;Keller AM;Joffre O;Zelenay S;Nye E;Le Moine A;Faure F;Donckier V;Sancho D;Cerundolo V;Bonnet D;Reis e Sousa C
通讯作者：
Reis e Sousa C
影响因子：
19.6
作者：
Soos, T. J.;Sims, T. N.;Nelson, P. J.
通讯作者：
Nelson, P. J.
影响因子：
4.4
作者：
Wan, Suigui;Xia, Changqing;More, Laurence
通讯作者：
More, Laurence