From the Neuroimmunology and MS Research (T.L., W.F., J.R., M.J.D., R.M.), Neurology Clinic, University Hospital Zurich; Division of Immunology (T.L.), University Children's Hospital Zurich, University of Zurich; Cellerys AG (W.F., R.M.), Schlieren, Switzerland; Immunity and Cancer (U932) (W.F.), Immune Response to Cancer Laboratory, Institut Curie, 26 rue d'Ulm, CEDEX 05, Paris, France; Functional Genomics Center Zurich (L.O.), Swiss Federal Institute of Technology and University of Zurich; Institute of Experimental Immunology (R.M.), University of Zurich, Switzerland; and Therapeutic Design Unit (R.M.), Center for Molecular Medicine, Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
Neurol Neuroimmunol Neuroinflamm. 2024 Jul;11(4):e200251. doi: 10.1212/NXI.0000000000200251. Epub 2024 Jun 4.
Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the CNS. It is the leading cause of chronic neurologic disability in young adults. Proinflammatory B cells and autoreactive T cells both play important roles in its pathogenesis. We aimed to study alterations of regulatory T cells (Tregs), which likely also contribute to the disease, but their involvement is less clear.
By combining multiple experimental approaches, we examined the Treg compartments in 41 patients with relapsing-remitting MS and 17 healthy donors.
Patients with MS showed a reduced frequency of CD4 T cells and Foxp3+ Tregs and age-dependent alterations of Treg subsets. Treg suppressive function was compromised in patients, who were treated with natalizumab, while it was unaffected in untreated and anti-CD20-treated patients. The changes in natalizumab-treated patients included increased proinflammatory cytokines and an altered transcriptome in thymus-derived (t)-Tregs, but not in peripheral (p)-Tregs.
Treg dysfunction in patients with MS might be related to an altered transcriptome of t-Tregs and a proinflammatory environment. Our findings contribute to a better understanding of Tregs and their subtypes in MS.
多发性硬化症（MS）被认为是中枢神经系统的典型自身免疫性疾病。它是导致年轻人慢性神经功能障碍的主要原因。促炎 B 细胞和自身反应性 T 细胞在其发病机制中都发挥着重要作用。我们旨在研究调节性 T 细胞（Tregs）的变化，这些细胞可能也与疾病有关，但它们的参与尚不清楚。
通过结合多种实验方法，我们研究了 41 名复发缓解型多发性硬化症患者和 17 名健康供体的 Treg 区室。
MS 患者的 CD4 T 细胞和 Foxp3+ Tregs 频率降低，Treg 亚群出现年龄依赖性改变。在接受那他珠单抗治疗的患者中，Treg 的抑制功能受损，而在未接受治疗和接受抗 CD20 治疗的患者中则不受影响。在接受那他珠单抗治疗的患者中，变化包括促炎细胞因子增加和胸腺来源（t）-Tregs 的转录组改变，但外周（p）-Tregs 不受影响。
MS 患者 Treg 功能障碍可能与 t-Tregs 的转录组改变和促炎环境有关。我们的发现有助于更好地理解 MS 中的 Tregs 及其亚型。
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