人神经干细胞抗原的呈递驱动调节性 T 细胞的诱导。
Presentation of Human Neural Stem Cell Antigens Drives Regulatory T Cell Induction.
机构信息
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA.
Department of Biological Chemistry, University of California, Irvine, Irvine, CA.
出版信息
J Immunol. 2023 Jun 1;210(11):1677-1686. doi: 10.4049/jimmunol.2200798.
Transplantation of human neural stem cells (hNSCs) is a promising regenerative therapy to promote remyelination in patients with multiple sclerosis (MS). Transplantation of hNSCs has been shown to increase the number of CD4+CD25+Foxp3+ T regulatory cells (Tregs) in the spinal cords of murine models of MS, which is correlated with a strong localized remyelination response. However, the mechanisms by which hNSC transplantation leads to an increase in Tregs in the CNS remains unclear. We report that hNSCs drive the conversion of T conventional (Tconv) cells into Tregs in vitro. Conversion of Tconv cells is Ag driven and fails to occur in the absence of TCR stimulation by cognate antigenic self-peptides. Furthermore, CNS Ags are sufficient to drive this conversion in the absence of hNSCs in vitro and in vivo. Importantly, only Ags presented in the thymus during T cell selection drive this Treg response. In this study, we investigate the mechanisms by which hNSC Ags drive the conversion of Tconv cells into Tregs and may provide key insight needed for the development of MS therapies.
人神经干细胞（hNSCs）移植是一种很有前途的再生疗法，可促进多发性硬化症（MS）患者的髓鞘再生。研究表明，hNSCs 移植可增加 MS 动物模型脊髓中 CD4+CD25+Foxp3+T 调节性细胞（Tregs）的数量，这与强烈的局部髓鞘再生反应相关。然而，hNSC 移植导致中枢神经系统中 Tregs 增加的机制尚不清楚。我们报告 hNSCs 可在体外将 T 常规（Tconv）细胞转化为 Tregs。Tconv 细胞的转化是 Ag 驱动的，如果没有 TCR 对同源抗原自身肽的刺激，则不会发生转化。此外，在体外和体内，中枢神经系统抗原足以在没有 hNSC 的情况下驱动这种转化。重要的是，只有在 T 细胞选择过程中胸腺中呈现的 Ag 才能驱动这种 Treg 反应。在这项研究中，我们研究了 hNSC Ag 驱动 Tconv 细胞转化为 Tregs 的机制，这可能为开发 MS 治疗方法提供所需的关键见解。
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