自身免疫
视神经脊髓炎
神经炎症
免疫疗法
免疫学
细胞毒性T细胞
CD8型
医学
抗原
多发性硬化
生物
癌症研究
T细胞
炎症
免疫系统
体外
生物化学
嵌合抗原受体
作者
Chuan Qin,Min Zhang,Dapeng Mou,Luo‐Qi Zhou,Minghao Dong,Liang Huang,Wen Wang,Song-Bai Cai,Yun‐Fan You,Ke Shang,Jun Xiao,Di Wang,Chunrui Li,Yi Hao,Michael Heming,Long‐Jun Wu,Gerd Meyer zu Hörste,Chen Dong,Bing Bu,De An Tian,Wei Wang
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2024-05-10
卷期号:9 (95)
标识
DOI:10.1126/sciimmunol.adj9730
摘要
Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti–B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8 + CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.
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