Prevention and treatment of experimental autoimmune encephalomyelitis with clonotypic CDR3 peptides: CD4(+) Foxp3(+) T-regulatory cells suppress interleukin-2-dependent expansion of myelin basic protein-specific T cells.
Prevention and treatment of experimental autoimmune encephalomyelitis with clonotypic CDR3 peptides: CD4(+) Foxp3(+) T-regulatory cells suppress interleukin-2-dependent expansion of myelin basic protein-specific T cells.
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使用克隆型 CDR3 肽预防和治疗实验性自身免疫性脑脊髓炎：CD4( ) Foxp3( ) T 调节细胞抑制髓磷脂碱性蛋白特异性 T 细胞的白细胞介素 2 依赖性扩增。
DOI：
10.1111/j.1365-2567.2009.03218.x
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发表时间：
2010
期刊：
影响因子：
6.4
通讯作者：
Vandenbark,ArthurA
中科院分区：
文献类型：
--
作者：
Buenafe,AbigailC;Andrew,Shayne;Afentoulis,Michael;Offner,Halina;Vandenbark,ArthurA
T细胞受体（TCR）衍生的肽被免疫系统识别，能够调节自身免疫反应。利用髓鞘碱性蛋白（MBP） TCR 1501转基因小鼠模型，我们证明了在诱导实验性自身免疫性脑脊髓炎（EAE）之前开始治疗时，来自转基因TCR的TCR CDR3肽可以提供保护作用。更重要的是，在EAE发病后给予TCR CDR3肽治疗可以改善疾病。在治疗效果的同时，我们观察到，与对照小鼠相比，接受TCR CDR3肽的小鼠脾细胞培养物中，MBP - 85 - 99肽刺激后，T细胞增殖和白细胞介素- 2 （IL - 2）水平降低。此外，我们发现受TCR CDR3肽保护的小鼠Foxp3+CD4 T细胞在IL‐2存在下优先扩增。这支持了一种被提出的机制，即MBP‐85‐99 TCR CDR3肽治疗诱导的Foxp3+T -调节性细胞通过调节分泌IL‐2的水平来限制MBP‐85‐99特异性T细胞的扩增和致脑活性。
T‐cell receptor (TCR)‐derived peptides are recognized by the immune system and are capable of modulating autoimmune responses. Using the myelin basic protein (MBP) TCR 1501 transgenic mouse model, we demonstrated that TCR CDR3 peptides from the transgenic TCR can provide a protective effect when therapy is initiated before the induction of experimental autoimmuneencephalomyelitis(EAE). More importantly, TCR CDR3 peptide therapy can ameliorate the disease when administered after EAE onset. Concurrent with the therapeutic effects, we observed reduced T‐cell proliferation and reduced interleukin‐2 (IL‐2) levels in response to stimulation with MBP‐85‐99 peptide in splenocyte cultures from mice receiving TCR CDR3 peptides compared with that of control mice. Moreover, we found that Foxp3+CD4 T cells from mice protected with TCR CDR3 peptide are preferentially expanded in the presence of IL‐2. This is supportive of a proposed mechanism where Foxp3+T‐regulatory cells induced by therapy with MBP‐85‐99 TCR CDR3 peptides limit expansion and the encephalitogenic activity of MBP‐85‐99‐specific T cells by regulating the levels of secreted IL‐2.