Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Am J Pathol. 2011 Oct;179(4):2028-41. doi: 10.1016/j.ajpath.2011.06.006. Epub 2011 Aug 26.
In multiple sclerosis (MS), myelin-specific T cells are normally associated with destruction of myelin and axonal damage. However, in acute MS plaque, remyelination occurs concurrent with T-cell infiltration, which raises the question of whether T cells might stimulate myelin repair. We investigated the effect of myelin-specific T cells on oligodendrocyte formation at sites of axonal damage in the mouse hippocampal dentate gyrus. Infiltrating T cells specific for myelin proteolipid protein stimulated proliferation of chondroitin sulfate NG2-expressing oligodendrocyte precursor cells early after induction via axonal transection, resulting in a 25% increase in the numbers of oligodendrocytes. In contrast, T cells specific for ovalbumin did not stimulate the formation of new oligodendrocytes. In addition, infiltration of myelin-specific T cells enhanced the sprouting response of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system.
在多发性硬化症 (MS) 中,髓鞘特异性 T 细胞通常与髓鞘破坏和轴突损伤有关。然而,在急性 MS 斑块中,髓鞘再生与 T 细胞浸润同时发生,这就提出了一个问题,即 T 细胞是否可能刺激髓鞘修复。我们研究了髓鞘特异性 T 细胞在小鼠海马齿状回轴突损伤部位对少突胶质细胞形成的影响。在通过轴突横断诱导后早期,针对髓鞘蛋白脂质蛋白的浸润 T 细胞刺激软骨素硫酸 NG2 表达的少突胶质前体细胞的增殖,导致少突胶质细胞数量增加 25%。相比之下,针对卵清蛋白的 T 细胞不会刺激新的少突胶质细胞形成。此外,髓鞘特异性 T 细胞的浸润增强了齿状回内钙结合蛋白阳性关联/连合纤维的发芽反应。这些结果对 MS 发病机制的认识具有重要意义,因为它们表明浸润的髓鞘特异性 T 细胞可以刺激成年中枢神经系统中的少突胶质细胞发生。