Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University Medical Center, Columbus, OH 43210, USA.
J Immunol. 2010 May 15;184(10):5628-36. doi: 10.4049/jimmunol.1000288. Epub 2010 Apr 14.
Myelin-specific effector Th1 cells are able to perpetuate CNS inflammation in experimental autoimmune encephalomyelitis, an animal model representative of multiple sclerosis. Although the effects of cytokines in the CNS microenvironment on naive CD4(+) T cells have been well described, much less is known about their ability to influence Ag-experienced effector cells. TGF-beta is a multifunctioning cytokine present in the healthy and inflamed CNS with well-characterized suppressive effects on naive T cell functions. However, the effects of TGF-beta on effector Th1 cells are not well defined. Using myelin-specific TCR transgenic mice, we demonstrate that TGF-beta elicits differential effects on naive versus effector Th1 cells. TGF-beta enhances cellular activation, proliferation, and cytokine production of effector Th1 cells; however, adoptive transfer of these cells into naive mice showed a reduction in encephalitogenicity. We subsequently demonstrate that the reduced encephalitogenic capacity is due to the ability of TGF-beta to promote the self-regulation of Th1 effector cells via IL-10 production. These data demonstrate a mechanism by which TGF-beta is able to suppress the encephalitogenicity of myelin-specific Th1 effector cells that is unique from its suppression of naive T cells.
髓鞘特异性效应 Th1 细胞能够在实验性自身免疫性脑脊髓炎（多发性硬化症的动物模型）中使中枢神经系统炎症持续存在。虽然中枢神经系统微环境中的细胞因子对幼稚 CD4(+)T 细胞的影响已得到很好的描述，但对其影响抗原特异性效应细胞的能力知之甚少。TGF-β是一种存在于健康和炎症中枢神经系统中的多功能细胞因子，对幼稚 T 细胞功能具有明显的抑制作用。然而，TGF-β对效应 Th1 细胞的作用尚未得到很好的定义。使用髓鞘特异性 TCR 转基因小鼠，我们证明 TGF-β对幼稚 Th1 细胞与效应 Th1 细胞的作用不同。TGF-β增强了效应 Th1 细胞的细胞活化、增殖和细胞因子产生；然而，将这些细胞过继转移到幼稚小鼠中，其致脑炎能力降低。我们随后证明，这种致脑炎能力的降低是由于 TGF-β通过产生 IL-10 促进 Th1 效应细胞的自我调节所致。这些数据表明了一种机制，即 TGF-β能够抑制髓鞘特异性 Th1 效应细胞的致脑炎能力，这与它抑制幼稚 T 细胞的机制不同。
