Nitric-oxide-dependent and independent mechanisms of protection from CNS inflammation during Th1-mediated autoimmunity: evidence from EAE in NOSKO mice
Nitric-oxide-dependent and independent mechanisms of protection from CNS inflammation during Th1-mediated autoimmunity: evidence from EAE in NOSKO mice
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DOI：
10.1016/j.jneuroim.2004.11.004
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Wittmer, S
中科院分区：
文献类型：
--
作者：
Dalton, DK;Wittmer, S
实验性自身免疫性脑脊髓炎 (EAE) 疾病在 iNOS 缺陷 (KO) 小鼠中加速：与外周 Ag 特异性 Th1 细胞数量大幅增加相一致，这些细胞在疾病症状出现期间似乎从脾脏迅速转移到 CNS。与野生型小鼠相比，iNOS KO 小鼠中枢神经系统中的 Th1 细胞显着增加。 iNOS KO小鼠在疾病高峰期中枢神经系统浸润的CD4(+) T细胞凋亡受损；因此，这些小鼠具有更多的 CNS 浸润 CD4(+) T 细胞。随后，iNOS KO 小鼠上调 CNS-CD4(+) T 细胞凋亡。慢性EAE期间，中枢神经系统巨噬细胞大大减少，表明中枢神经系统浸润的CD4+T细胞和活化的巨噬细胞通过iNOS独立机制被消除。 INOS不仅是CNS-CD4(+) T细胞凋亡所必需的，而且还可以防止外周和CNS中自身反应性Th1细胞的过度扩张。 (c) 2004 Elsevier B.V. 保留所有权利。
Experimental autoimmune encephalomyelitis (EAE) disease was accelerated iNOS-deficient (KO) mice: coinciding with greatly increased numbers of Ag-specific Th1 cells in the periphery that appeared to rapidly shift from the spleen to the CNS during onset of disease symptoms. iNOS KO mice had significantly increased Th1 cells in the CNS versus wild-type mice. Apoptosis of CNS-infiltrating CD4(+) T cells was impaired in iNOS KO mice at peak of disease; consequently, these mice had more CNS-infiltrating CD4(+) T cells. Subsequently, iNOS KO mice up-regulated apoptosis of CNS-CD4(+) T cells. During chronic EAE, CNS macrophages were greatly decreased, suggesting elimination of CNS-infiltrating CD4(+) T cells and activated macrophages by iNOS-independent mechanisms. INOS is not only required for apoptosis of CNS-CD4(+) T cells but also prevents overexpansion of autoreactive Th1 cells in the periphery and the CNS. (c) 2004 Elsevier B.V. All rights reserved.