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复发缓解型多发性硬化症患者 T 细胞及细胞因子谱失衡。

Imbalance in T-cell and cytokine profiles in patients with relapsing-remitting multiple sclerosis.

机构信息

University Cell Immunotherapy Center, Babak Research Institute, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Republic.

出版信息

J Neurol Sci. 2011 Jan 15;300(1-2):135-41. doi: 10.1016/j.jns.2010.08.053.

Abstract

Multiple sclerosis (MS) is characterized by autoimmune attack leading to demyelination of the white matter in the central nervous system with devastating clinical consequences. Several immune-mediated destruction mechanisms were previously proposed including different T-cell subsets but complex view on immune system function in patients with MS is missing. In the present study, T-lymphocyte populations and pro-inflammatory as well as suppressive cytokine profiles were evaluated in detail in previously untreated patients with relapsing-remitting MS (RRMS). CD4(+) and CD8(+) naïve, central memory (Tcm), effector memory (Tem), terminal effector memory (Ttem), CD4(+) regulatory T-cells (Treg) and CD8(+) T-suppressor cells (Ts) were analysed using flow cytometry, and levels of ten plasma cytokines were determined using fluorescent bead-based immunoassay. We evaluated two groups of RRMS with minor (n=33) and major (n=25) clinical impairment and compared them with healthy controls (n=40) in order to detect any correlation between severity of MS clinical symptoms and immune disturbances. Significant differences were noted in CD4(+)CD45RA(+)CCR7(+) naïve T-cells, CD4(+)CD45RO(+)CCR7(-) and CD8(+)CD45RO(+)CCR7(-) Tem cells, while no differences were recognized in Tcm, Ttem, Treg and Ts cells in RRMS patients. Nine out of ten studied cytokines were disturbed in plasma samples of patients with RRMS. In conclusion, we demonstrate complex immune dysbalances in untreated MS patients.

摘要

多发性硬化症(MS)的特征是自身免疫攻击导致中枢神经系统白质脱髓鞘,具有破坏性的临床后果。以前提出了几种免疫介导的破坏机制,包括不同的 T 细胞亚群,但对 MS 患者免疫系统功能的复杂观点仍然缺乏。在本研究中,我们详细评估了未经治疗的复发缓解型多发性硬化症(RRMS)患者的 T 淋巴细胞群以及前炎症和抑制性细胞因子谱。使用流式细胞术分析 CD4(+)和 CD8(+)幼稚、中央记忆 (Tcm)、效应记忆 (Tem)、终末效应记忆 (Ttem)、CD4(+)调节性 T 细胞 (Treg)和 CD8(+)T 抑制细胞 (Ts),并使用荧光珠基于免疫测定法测定十种血浆细胞因子的水平。我们评估了两组具有轻度(n=33)和重度(n=25)临床损伤的 RRMS 患者,并将其与健康对照组(n=40)进行比较,以检测 MS 临床症状严重程度与免疫紊乱之间的任何相关性。在 CD4(+)CD45RA(+)CCR7(+)幼稚 T 细胞、CD4(+)CD45RO(+)CCR7(-)和 CD8(+)CD45RO(+)CCR7(-) Tem 细胞中观察到显著差异,而在 Tcm、Ttem、Treg 和 Ts 细胞中未观察到差异。在 RRMS 患者的血浆样本中,有九种研究的细胞因子存在紊乱。总之,我们证明了未经治疗的 MS 患者存在复杂的免疫失衡。

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