biostudies-literatureYang TTthe Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education6262https://www.ebi.ac.uk/biostudies/studies/S-EPMC10943184biostudies-literatureUnknown14(1)CD4⁺CD25⁺ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4⁺CD25^highCD127^low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 10⁴ cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS.Scientific reportsCD4⁺CD25⁺ regulatory T cells ex vivo generated from autologous naive CD4⁺ T cells suppress EAE progression.PMC10943184KZ201910025030Ma LYuan GBLi QLiu PJYang TTZou WLYuan BYLiu GZFan ZXLu JFZhao LMSun QYWang ZYfalseCD4⁺CD25⁺ regulatory T cells ex vivo generated from autologous naive CD4⁺ T cells suppress EAE progression.CD4⁺CD25⁺ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4⁺CD25^highCD127^low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 10⁴ cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS.2024-01-01T00:00:00Z2024 Mar2026-06-28T03:18:49.02Z2025-04-07T00:15:22.921ZS-EPMC109431843849108410.1038/s41598-024-56739-2