Unlike Th1, Th17 cells mediate sustained autoimmune inflammation and are highly resistant to restimulation-induced cell death.
Unlike Th1, Th17 cells mediate sustained autoimmune inflammation and are highly resistant to restimulation-induced cell death.
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DOI：
10.4049/jimmunol.0900519
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发表时间：
2009-12-01
期刊：
影响因子：
--
通讯作者：
Gery I
中科院分区：
文献类型：
--
作者：
Shi G;Ramaswamy M;Vistica BP;Cox CA;Tan C;Wawrousek EF;Siegel RM;Gery I
Th 1和Th 17 T细胞亚群都可以介导炎症，但这两个亚群介导的致病过程的动力学尚未研究。使用一个实验系统，其中TCR-转基因的Th 1或Th 17细胞特异性鸡蛋溶菌酶诱导受体小鼠表达眼限制性鸡蛋溶菌酶眼部炎症，我们发现这两个子集的体内行为的重要差异。Th 1细胞最初的增殖速度比Th 17细胞快得多，侵入眼睛的速度也比Th 17细胞快得多，但随后迅速消失。相比之下，Th 17细胞在转移后长达25天的时间内积累并保持为眼睛中浸润性CD 4+细胞的大多数，介导更持久的病理变化。与Th 1细胞不同，Th 17细胞对再刺激诱导的细胞凋亡具有高度抗性，这是消除自身免疫性和慢性再刺激的Th 1细胞的主要途径。Th 17细胞减少Fas配体的产生和抵抗Fas诱导的凋亡，相对于Th 1细胞，尽管相似的表面表达Fas。Th 17诱导的眼部炎症也不同于Th 1诱导的炎症，由更多的中性粒细胞组成，而Th 1诱导的疾病具有更高比例的CD 8细胞。总之，我们的数据表明，Th 17触发的致病过程滞后于Th 1诱导的致病过程，但随后持续时间明显更长，这显然是由于Th 17细胞对再刺激诱导的细胞死亡的相对抗性。由Th 17细胞诱导的持久炎症与这些细胞参与人类慢性病症是雅阁的。
Both Th1 and Th17 T cell subsets can mediate inflammation, but the kinetics of the pathogenic processes mediated by these two subsets have not been investigated. Using an experimental system in which TCR-transgenic Th1 or Th17 cells specific for hen egg lysozyme induce ocular inflammation in recipient mice expressing eye-restricted hen egg lysozyme, we found important differences in the in vivo behavior of these two subsets. Th1 cells initially proliferated considerably faster and invaded the eye more quickly than their Th17 counterparts, but then disappeared rapidly. By contrast, Th17 cells accumulated and remained the majority of the infiltrating CD4+ cells in the eye for as long as 25 days after transfer, mediating more long-lasting pathological changes. Unlike Th1, Th17 cells were highly resistant to restimulation-induced apoptosis, a major pathway by which autoimmune and chronically restimulated Th1 cells are eliminated. Th17 cells had reduced Fas ligand production and resistance to Fas-induced apoptosis, relative to Th1 cells, despite similar surface expression of Fas. Th17-induced ocular inflammation also differed from Th1-induced inflammation by consisting of more neutrophils, whereas Th1-induced disease had higher proportions of CD8 cells. Taken together, our data show that pathogenic processes triggered by Th17 lag behind those induced by Th1, but then persist remarkably longer, apparently due to the relative resistance of Th17 cells to restimulation-induced cell death. The long-lasting inflammation induced by Th17 cells is in accord with these cells being involved in chronic conditions in humans.
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DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
4.4
作者：
Dalton, JE;Howell, G;Carding, SR
通讯作者：
Carding, SR
影响因子：
56.9
作者：
KATZ, JD;BENOIST, C;MATHIS, D
通讯作者：
MATHIS, D
在 Vogt-Koyanagi-Harada 病中，IL-23 促进 CD4 T 细胞产生 IL-17。
影响因子：
14.2
作者：
Chi, Wei;Yang, Peizeng;Kijlstra, Aize
通讯作者：
Kijlstra, Aize
影响因子：
30.5
作者：
Ilarregui, Juan M.;Croci, Diego O.;Rabinovich, Gabriel A.
通讯作者：
Rabinovich, Gabriel A.