An organic CD4 inhibitor reduces the clinical and pathological symptoms of acute experimental allergic encephalomyelitis
An organic CD4 inhibitor reduces the clinical and pathological symptoms of acute experimental allergic encephalomyelitis
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DOI：
10.1006/jaut.2001.0576
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发表时间：
2002-03-01
影响因子：
12.8
通讯作者：
Korngold, R
中科院分区：
文献类型：
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作者：
Edling, AE;Choksi, S;Korngold, R
CD4+T细胞在介导许多人类和实验性自身免疫性疾病的发病机制中发挥重要作用，包括实验性过敏性脑脊髓炎（EAE），一种多发性硬化症（MS）的脱髓鞘动物模型。我们应用计算机筛选方法来选择一种有机小分子 TJU103，它可以通过破坏 CD4 分子在激活过程中的功能来特异性抑制自身反应性 CD4(+) T 细胞。在研究 TJU103 对急性 EAE 的治疗效果后发现，在 SJL 和 SWXJ-14 小鼠模型中，在临床症状出现之前或之后不久给药可减轻疾病的严重程度。此外，TJU103治疗可能影响对EAE再攻击的体内反应以及对蛋白脂质蛋白表位139-151 (PLPe)作出反应的T细胞的继发性体外增殖和细胞因子产生。这些结果证明了 TJU103 有机抑制剂在未来临床应用中治疗 CD4(+) T 细胞介导的疾病的潜力。 (C) 2002 爱思唯尔科学有限公司。
CD4(+) T cells have an important role in mediating the pathogenesis of many human and experimental autoimmune diseases including experimental allergic encephalomyelitis (EAE), a demyelinating animal model for multiple sclerosis (MS). We applied a computer screening approach to select a small organic molecule, TJU103, that would specifically inhibit autoreactive CD4(+) T cells by disrupting the function of the CD4 molecule during activation. Upon studying the therapeutic effect of TJU103 in acute EAE, it was found that administration shortly before or after the onset of clinical symptoms reduced the severity of disease in both SJL and SWXJ-14 mouse models. In addition, TJU103 treatment could affect both in vivo responses to EAE rechallenge and secondary in vitro proliferation and cytokine production of T cells responding to proteolipid protein epitope 139-151 (PLPe). These results demonstrate the potential of the TJU103 organic inhibitor for future clinical application in CD4(+) T cell-mediated diseases. (C) 2002 Elsevier Science Ltd.