Department of Pathology, University of Utah, Salt Lake City, UT 84132, United States.
J Neuroimmunol. 2012 Mar;244(1-2):35-44. doi: 10.1016/j.jneuroim.2011.12.024. Epub 2012 Jan 14.
Immune-mediated diseases [multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE)] are driven by proliferating, highly activated autoreactive T-cells that are unresponsive to in vivo immunoregulatory mechanisms. The compound Lenaldekar (LDK) was identified in a zebrafish screen by inhibiting T-cell expansion. By monitoring mitogen- and antigen-driven proliferation, we found that LDK inhibited human and murine T-cell expansion in a non-cytolytic manner. This suppressive activity directly correlated with the degree of activation/proliferation of the T-cells. In testing LDK in an EAE model of MS, exacerbations were suppressed in treated animals. Therefore, LDK represents a novel therapeutic approach to T-cell-mediated autoimmune diseases.
免疫介导的疾病（多发性硬化症[MS]，实验性自身免疫性脑脊髓炎[EAE]）是由增殖的、高度活化的自身反应性 T 细胞驱动的，这些细胞对体内免疫调节机制无反应。化合物 Lenaldekar（LDK）是通过抑制 T 细胞扩增在斑马鱼筛选中鉴定出来的。通过监测有丝分裂原和抗原驱动的增殖，我们发现 LDK 以非细胞毒性方式抑制人和鼠 T 细胞的扩增。这种抑制活性与 T 细胞的激活/增殖程度直接相关。在 MS 的 EAE 模型中测试 LDK 时，治疗动物的恶化得到了抑制。因此，LDK 代表了一种治疗 T 细胞介导的自身免疫性疾病的新方法。
