Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). MS is thought to be T-cell-mediated, with prior research predominantly focusing on CD4+ T-cells. There is a high prevalence of CNS-specific CD8+ T-cell responses in MS patients and healthy subjects. However, the role of neuroantigen-specific CD8+ T-cells in MS is poorly understood, with the prevalent notion that these may represent pathogenic T-cells. We show here that healthy subjects and MS patients demonstrate similar magnitudes of CD8+ and CD4+ T-cell responses to various antigenic stimuli. Interestingly, CD8+ T-cells specific for CNS autoantigens, but not those specific for control foreign antigens, exhibit immune regulatory ability, suppressing proliferation of CD4+CD25- T-cells when stimulated by their cognate antigen. While CD8+ T-cell-mediated immune suppression is similar between healthy subjects and clinically quiescent treatment-naïve MS patients, it is significantly deficient during acute exacerbation of MS. Of note, the recovery of neuroantigen-specific CD8+ T-cell suppression correlates with disease recovery post-relapse. These studies reveal a novel immune suppressor function for neuroantigen-specific CD8+ T-cells that is clinically relevant in the maintenance of peripheral tolerance and the intrinsic regulation of MS immune pathology.

译文

:多发性硬化症(MS)是中枢神经系统(CNS)的一种炎症性脱髓鞘疾病。 MS被认为是T细胞介导的,先前的研究主要集中在CD4 T细胞上。在MS患者和健康受试者中,CNS特异性CD8 T细胞反应的发生率很高。然而,人们对神经抗原特异性CD8 T细胞在MS中的作用了解甚少,普遍认为它们可能代表致病性T细胞。我们在这里显示健康的受试者和MS患者表现出相似程度的CD8和CD4 T细胞对各种抗原刺激的反应。有趣的是,对CNS自身抗原具有特异性的CD8 T细胞(而非对控制外源抗原具有特异性的CD8 T细胞)具有免疫调节能力,当受到其同源抗原刺激时抑制CD4 CD25-T细胞的增殖。尽管健康受试者和未经临床治疗的MS患者之间CD8 T细胞介导的免疫抑制作用相似,但在MS急性加重期间,CD8 T细胞介导的免疫抑制作用明显不足。值得注意的是,神经抗原特异性CD8 T细胞抑制的恢复与复发后疾病的恢复相关。这些研究揭示了神经抗原特异性CD8 T细胞的新型免疫抑制功能,在维持外周耐受和MS免疫病理的内在调节方面具有临床意义。

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