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Updated: Aug 6, 2026
Flow Cytometric Analysis of Lymphocyte Infiltration in Central Nervous System during Experimental Autoimmune Encephalomyelitis
Published on: November 17, 2020
CNS immune remodelling in SLE associated with anti-CD19 CAR-T therapy
Jinjian Sun1, Xiaoru Hu2, Weina Li3
1Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of General &Vascular Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Objectives:
Autologous anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy shows promise for refractory systemic lupus erythematosus (SLE), but its impact on central nervous system (CNS) immune remodelling and the cellular features associated with CAR-T-associated neurotoxicity remains unclear.
Methods:
We performed integrated single‑cell RNA/T-cell receptor (TCR) sequencing and Olink proteomics on cerebrospinal fluid (CSF) from patients with SLE treated longitudinally with CAR‑T therapy (baseline n = 2, D9 n = 4, D60 n = 5), plus independent baseline single-cell RNA sequencing (n = 2) and Olink samples (n = 3).
Results:
Single-cell profiling of 47,222 CSF cells showed dynamic CNS immune composition following CAR-T therapy, with notable changes in T cells. CAR-T cells were detected in the CNS and displayed predominantly proliferative and cytotoxic states at D9, whereas memory- and exhaustion-associated states predominated at D60. Endogenous CD8⁺ T cells exhibited diverse effector subsets at day 9, including granzyme B (GZMB)⁺, natural killer-like, type I interferon (IFN)-responsive, and human leukocyte antigen (HLA)⁺ granzyme H (GZMH)⁺ populations, followed by predominance of memory and proliferating subsets at day 60. CD4⁺ T cells at day 9 were enriched for type I IFN signalling. Ligand-receptor analysis showed extensive interactions between myeloid populations and lymphocytes. TCR analysis showed changes in clonal diversity and dynamics following treatment.
Conclusions:
These findings suggest an association between CAR-T therapy and CNS immune remodelling in SLE, and provide cellular and molecular observations that may inform future studies of CNS immunity.
