Deshpande Pratima, King Irah L, Segal Benjamin M
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 605, Rochester, NY, 14642, USA.
J Neuroimmunol. 2006 Apr;173(1-2):35-44. doi: 10.1016/j.jneuroim.2005.11.016. Epub 2006 Jan 18.
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system. IL-12p40 monokines play a critical role in the generation of EAE-inducing CD4+T cells. Here we show that IL-12 directly upregulates the expression of the adhesion molecule, P-selectin glycoprotein ligand (PSGL-1), on B10.PL MBP-TCR transgenic T cells during their initial encounter with antigen. Pre-incubation of IL-12-stimulated myelin-reactive CD4+T cells with a blocking antibody against PSGL-1 reduced the incidence and severity of EAE. We conclude that IL-12-driven PSGL-1 expression can facilitate the development of autoimmune demyelination.
实验性自身免疫性脑脊髓炎(EAE)是一种中枢神经系统的炎性脱髓鞘疾病。白细胞介素-12p40单因子在诱导EAE的CD4⁺T细胞生成中起关键作用。在此我们表明,白细胞介素-12在B10.PL髓鞘碱性蛋白- TCR转基因T细胞初次接触抗原期间直接上调黏附分子P-选择素糖蛋白配体(PSGL-1)的表达。用抗PSGL-1阻断抗体对白细胞介素-12刺激的髓鞘反应性CD4⁺T细胞进行预孵育,可降低EAE的发病率和严重程度。我们得出结论,白细胞介素-12驱动的PSGL-1表达可促进自身免疫性脱髓鞘的发展。