Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis
Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis
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DOI：
10.1002/eji.200526065
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发表时间：
2005-11-01
影响因子：
5.4
通讯作者：
Wildemann, B
中科院分区：
文献类型：
--
作者：
Haas, J;Hug, A;Wildemann, B
CD4(+)CD25(+)表型的免疫调节T细胞抑制T细胞功能并保护啮齿动物免受器官特异性自身免疫性疾病的侵害。该 T 细胞亚群的人类对应物表达高水平的 CD25，其在人类自身免疫性疾病中的作用目前正在深入研究中。在多发性硬化症 (MS) 这种中枢神经系统 (CNS) 慢性炎症性疾病中，对髓磷脂成分具有特异性的循环自身反应性 T 细胞的激活被认为是重要的疾病起始事件。在此，我们研究了 MS 是否与 CD4(+)CD25(high) 调节性 T 细胞 (T-reg) 抑制髓磷脂特异性免疫反应的能力改变有关。虽然多发性硬化症患者的血液和脑脊液中 T-reg 频率均匀分布，与健康对照相比没有差异，但患者来源的 CD4(+)CD25(高) T 淋巴细胞的抑制效力受到损害。与健康个体相比，它们对人重组髓磷脂少突胶质细胞蛋白诱导的抗原特异性 T 细胞增殖以及多克隆和同种异体刺激引起的免疫反应的抑制作用显着降低。这种效应是持久的，并不是由于应答细胞抵抗或 T-reg 生存改变所致，表明 CD4(+)CD25(high) T 淋巴细胞介导的外周 T 细胞免疫调节缺陷促进了 MS 中的中枢神经系统自身免疫。
Immunoregulatory T cells of CD4(+)CD25(+) phenotype suppress T cell function and protect rodents from organ-specific autoimmune disease. The human counterpart of this subset of T cells expresses high levels of CD25 and its role in human autoimmune disorders is currently under intense investigation. In multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), the activation of circulating self-reactive T cells with specificity for myelin components is considered to be an important disease initiating event. Here, we investigated whether MS is associated with an altered ability of CD4(+)CD25(high) regulatory T cells (T-reg) to confer suppression of myelin-specific immune responses. Whereas T-reg frequencies were equally distributed in blood and cerebrospinal fluid of MS patients and did not differ compared to healthy controls, the suppressive potency of patient-derived CD4(+)CD25(high) T lymphocytes was impaired. Their inhibitory effect on antigen-specific T cell proliferation induced by human recombinant myelin oligodendrocyte protein as well as on immune responses elicited by polyclonal and allogeneic stimuli was significantly reduced compared to healthy individuals. The effect was persistent and not due to responder cell resistance or altered survival of T-reg, suggesting that a defective immunoregulation of peripheral T cells mediated by CD4(+)CD25(high) T lymphocytes promotes CNS autoimmunity in MS.