Interleukin-2/interleukin-2 antibody therapy induces target organ natural killer cells that inhibit central nervous system inflammation.
Interleukin-2/interleukin-2 antibody therapy induces target organ natural killer cells that inhibit central nervous system inflammation.
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DOI：
10.1002/ana.22339
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发表时间：
2011-04
影响因子：
11.2
通讯作者：
Shi, Fu-Dong
中科院分区：
文献类型：
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作者：
Hao, Junwei;Campagnolo, Denise;Liu, Ruolan;Piao, Wenhua;Shi, Samuel;Hu, Baoyang;Xiang, Rong;Zhou, Qinghua;Vollmer, Timothy;Van Kaer, Luc;La Cava, Antonio;Shi, Fu-Dong
自然杀伤 (NK) 细胞在调节多发性硬化症 (MS) 中的作用尚不清楚。对 NK 细胞的其他研究可能有助于深入了解 MS 疗法的作用机制，例如 daclizumab（一种针对 IL-2R α 链的抗体，可诱导 CD56bright NK 细胞的扩增）。在 SJL 小鼠中诱导的实验性自身免疫性脑脊髓炎 (EAE) 模型中，我们使用 IL-2 和抗 IL-2 mAb 扩增 NK 细胞，并评估这些 NK 细胞对 EAE 的影响。此外，我们在人-小鼠嵌合体模型中研究了人版 IL-2/IL-2 mAb 对 MS 患者 NK 细胞的影响及其对中枢神经系统炎症和病理学的影响，并评估了潜在机制。 IL-2/IL-2 mAb 可显着扩增外周淋巴器官和中枢神经系统 (CNS) 中的 NK 细胞，并减轻 CNS 炎症和神经功能缺损。疾病保护是由中枢神经系统驻留的 NK 细胞赋予的。重要的是，人类版本的 IL-2/IL-2 mAb 在人-小鼠嵌合模型中恢复了多发性硬化症患者的缺陷 CD56+ NK 细胞。在该模型中，需要 CD56bright 和 CD56dim 亚群来减轻疾病。这些发现揭示了 NK 细胞的免疫治疗潜力，NK 细胞可以作为自身免疫靶器官中的关键抑制细胞。这些结果还有助于更好地理解达珠单抗在多发性硬化症中的作用机制。
The role of natural killer (NK) cells in regulating multiple sclerosis (MS) is not well understood. Additional studies with NK cells might provide insight into the mechanism of action of MS therapies such as daclizumab, an antibody against the IL-2R α-chain, which induces expansion of CD56bright NK cells. In a relapsing-remitting form of the experimental autoimmune encephalomyelitis (EAE) model of MS induced in SJL mice, we expanded NK cells with IL-2 coupled with an anti-IL-2 mAb and evaluated the effects of these NK cells on EAE. Further, we investigated the effect of the human version of IL-2/IL-2 mAb on NK cells from MS patients and its effect on CNS inflammation and pathology in a human-mouse chimera model and assessed the underlying mechanisms. IL-2/IL-2 mAb dramatically expands NK cells both in the peripheral lymphoid organs and in the central nervous system (CNS), and attenuates CNS inflammation and neurological deficits. Disease protection is conferred by CNS-resident NK cells. Importantly, the human version of IL-2/IL-2 mAb restored the defective CD56+ NK cells from MS patients in a human-mouse chimera model. Both the CD56bright and CD56dim subpopulations were required to attenuate disease in this model. These findings unveil the immunotherapeutic potential of NK cells, which can act as critical suppressor cells in target organs of autoimmunity. These results also have implications to better understand the mechanism of action of daclizumab in MS.
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影响因子：
--
作者：
Bielekova, Bibiana;Howard, Thomas;Packer, Amy N.;Richert, Nancy;Blevins, Gregg;Ohayon, Joan;Waldmann, Thomas A.;McFarland, Henry F.;Martin, Roland
通讯作者：
Martin, Roland
DOI：
10.1073/pnas.0914732107
发表时间：
2010-02-09
影响因子：
11.1
作者：
Leavenworth, Jianmei W.;Schellack, Carola;Cantor, Harvey
通讯作者：
Cantor, Harvey
影响因子：
32.4
作者：
Mendiratta, SK;Martin, WD;VanKaer, L
通讯作者：
VanKaer, L
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
DOI：
10.1073/pnas.0601335103
发表时间：
2006-04-11
影响因子：
11.1
作者：
Bielekova, B;Catalfamo, M;Martin, R
通讯作者：
Martin, R