免疫学
达利珠单抗
实验性自身免疫性脑脊髓炎
单克隆抗体
炎症
白细胞介素15
免疫系统
自身免疫
生物
白细胞介素21
多发性硬化
Janus激酶3
抗体
白细胞介素
医学
细胞因子
T细胞
作者
Junwei Hao,Denise I. Campagnolo,Ruolan Liu,Wenhua Piao,Samuel Shi,Baoyang Hu,Rong Xiang,Qinghua Zhang,Timothy Vollmer,Luc Van Kaer,Antonio La Cava,Fu‐Dong Shi
摘要
Abstract Objective: 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 interleukin (IL)‐2R α‐chain, which induces expansion of CD56 bright NK cells. Methods: 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 monoclonal antibody (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 central nervous system (CNS) inflammation and pathology in a human–mouse chimera model and assessed the underlying mechanisms. Results: IL‐2/IL‐2 mAb dramatically expands NK cells both in the peripheral lymphoid organs and in the 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 CD56 bright and CD56 dim subpopulations were required to attenuate disease in this model. Interpretation: 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. Ann Neurol 2011;
科研通智能强力驱动
Strongly Powered by AbleSci AI