Cytokine switch and bystander suppression of autoimmune responses to multiple antigens in experimental autoimmune encephalomyelitis by a single recombinant T-cell receptor ligand.
Cytokine switch and bystander suppression of autoimmune responses to multiple antigens in experimental autoimmune encephalomyelitis by a single recombinant T-cell receptor ligand.
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DOI：
10.1523/jneurosci.5812-08.2009
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发表时间：
2009-03-25
期刊：
影响因子：
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通讯作者：
Offner H
中科院分区：
文献类型：
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作者：
Sinha S;Subramanian S;Miller L;Proctor TM;Roberts C;Burrows GG;Vandenbark AA;Offner H
重组T细胞受体配体（RTL）可以以抗原特异性方式逆转实验性自身免疫性脑脊髓炎（EAE）的临床和组织学体征，并且目前处于治疗多发性硬化（MS）受试者的临床试验中。RTL的抗原特异性提出了一个问题，即这种治疗在靶抗原未知的MS患者中是否会成功。使用脊髓匀浆或两种不同肽的组合来诱导疾病，我们发现只要靶向T细胞存在，用单一RTL治疗就可以逆转EAE。用三种不同的RTL治疗各自引起肽活化的脾细胞中IL-17的显著减少和IL-10和IL-13的增加，降低淋巴结细胞的同源和旁观者特异性的增殖，并且减少炎性病变和从肽活化的脊髓细胞分泌的IL-17和IL-2。这些结果表明，用单个RTL治疗可以诱导同源T细胞中的细胞因子转换，其抑制靶T细胞和旁观者T细胞，为RTL治疗在MS中的潜在适用性提供了新的证据。
Recombinant T-cell receptor ligands (RTLs) can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner, and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). Antigen specificity of RTL raises the question as to whether this treatment would be successful in MS patients where target antigens are unknown. Using spinal cord homogenate or combinations of two different peptides to induce disease,we found that treatment with single RTL could reverse EAE as long as targeted T-cells were present. Therapy with three different RTLs each caused a significant reduction in IL-17 and increases in IL-10 and IL-13 in peptide-activated splenocytes, reduced proliferation of both cognate and bystander specificities of lymph node cells, and reduced inflammatory lesions and secreted IL-17 and IL-2 from peptide-activated spinal cord cells. These results show that treatment with single RTLs can induce a cytokine switch in cognate T-cells that inhibits both the target and bystander T-cells, providing new evidence for the potential applicability of RTL therapy in MS.