Mazzeo Anna Chiara, Calabresi Laura, Damato Valentina, Spagni Gregorio, Massacesi Luca, Mariottini Alice
Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, 50139 Florence, Italy.
Department of Emergency Neurology, Careggi University Hospital, 50139 Florence, Italy.
Int J Mol Sci. 2025 Jul 11;26(14):6655. doi: 10.3390/ijms26146655.
The traditional paradigm of multiple sclerosis (MS) as a T cell-mediated disorder has been challenged by the effectiveness of monoclonal antibodies (mAbs) targeting CD20-expressing lymphocytes. Although these are mostly represented by B cells, the CD20 marker is expressed by 2-6% of T cells (CD20+ T), which are effectively depleted in serum and cerebrospinal fluid of MS patients by anti-CD20 mAbs. CD20+ T cells are characterized by a pro-inflammatory phenotype and increased potential for migrating and invading the central nervous system (CNS) compared to CD20- T cells. Furthermore, CD20+ T cells are detected within brain inflammatory lesions from MS patients and actively participate in the experimental MS model. This review aims to summarize the current knowledge on CD20+ T cells, from their identification and characterization to evidence of depletion by disease-modifying treatments (DMTs), likely contributing to therapeutic efficacy. Conflicting hypotheses on the origin and development of CD20+ T cells will also be discussed, as well as evidence from clinical and preclinical studies supporting their pathogenetic role in MS.
将多发性硬化症（MS）视为一种T细胞介导疾病的传统范式，已受到靶向表达CD20的淋巴细胞的单克隆抗体（mAb）有效性的挑战。虽然这些细胞大多为B细胞，但2%-6%的T细胞（CD20+T）也表达CD20标志物，抗CD20 mAb可有效清除MS患者血清和脑脊液中的这些细胞。与CD20-T细胞相比，CD20+T细胞具有促炎表型，迁移和侵入中枢神经系统（CNS）的能力增强。此外，在MS患者的脑炎性病变中可检测到CD20+T细胞，且它们积极参与实验性MS模型。本综述旨在总结目前关于CD20+T细胞的知识，从其识别和特征到疾病修饰治疗（DMT）导致其耗竭的证据，这可能有助于治疗效果。还将讨论关于CD20+T细胞起源和发育的相互矛盾的假说，以及临床和临床前研究支持它们在MS发病机制中作用的证据。
