淋巴细胞性脉络膜脑膜炎
CD8型
免疫学
细胞毒性T细胞
免疫系统
炎症
生物
中枢神经系统
抗原
免疫病理学
神经科学
体外
生物化学
作者
Ilena Vincenti,Nicolas Pagé,Karin Steinbach,Alexander Yermanos,Sylvain Lemeille,Nicolás Gonzalo Núñez,Mario Kreutzfeldt,Bogna Klimek,Giovanni Di Liberto,Kristóf Égervári,Margot Piccinno,Ghazal Shammas,Alexandre Mariotte,Nicolas Fonta,Nicolas Liaudet,Danielle Shlesinger,Anna Rita Liuzzi,Ingrid Wagner,Cynthia Saadi,Christine Stadelmann,Sai T. Reddy,Burkhard Becher,Doron Merkler
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2022-04-13
卷期号:14 (640)
被引量:34
标识
DOI:10.1126/scitranslmed.abl6058
摘要
In chronic inflammatory diseases of the central nervous system (CNS), immune cells persisting behind the blood-brain barrier are supposed to promulgate local tissue destruction. The drivers of such compartmentalized inflammation remain unclear, but tissue-resident memory T cells (T RM ) represent a potentially important cellular player in this process. Here, we investigated whether resting CD8 + T RM persisting after cleared infection with attenuated lymphocytic choriomeningitis virus (LCMV) can initiate immune responses directed against cognate self-antigen in the CNS. We demonstrated that time-delayed conditional expression of the LCMV glycoprotein as neo-self-antigen by glia cells reactivated CD8 + T RM . Subsequently, CD8 + T RM expanded and initiated CNS inflammation and immunopathology in an organ-autonomous manner independently of circulating CD8 + T cells. However, in the absence of CD4 + T cells, TCF-1 + CD8 + T RM failed to expand and differentiate into terminal effectors. Similarly, in human demyelinating CNS autoimmune lesions, we found CD8 + T cells expressing TCF-1 that predominantly exhibited a T RM -like phenotype. Together, our study provides evidence for CD8 + T RM -driven CNS immunopathology and sheds light on why inflammatory processes may evade current immunomodulatory treatments in chronic autoimmune CNS conditions.
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