Samoilova E B, Horton J L, Chen Y
Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA.
Cell Immunol. 1998 Sep 15;188(2):118-24. doi: 10.1006/cimm.1998.1365.
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) which is often used as an animal model for human multiple sclerosis (MS). The disease is mediated by autoreactive lymphocytes recognizing myelin self-antigens. The autoreactive lymphocytes elicit autoimmune inflammation in the CNS and lead to demyelination and loss of neurological functions. Although autoimmune encephalomyelitis can lead to irreversible nervous tissue injury and demise of animals, EAE is often characterized by spontaneous disease recovery or remission. It is not known how EAE progression is regulated, nor is it clear how autoimmune inflammation in the CNS can resolve while the myelin-specific lymphocytes and myelin self-antigens remain in the animals. Cytokines, especially TH2-type cytokines, have long been suggested to play a role in regulating EAE. However, experiments using recombinant cytokines or neutralizing antibodies to cytokines have generated conflicting results. To determine the roles of interleukin (IL)-4 and IL-10 in experimental autoimmune encephalomyelitis, we have studied mice deficient in IL-4 or IL-10. We found that IL-10- but not IL-4-deficient mice had accelerated EAE following immunization with myelin oligodendrocyte glycoprotein (MOG). Importantly, spontaneous recovery from EAE occurred in normal and IL-4-deficient mice, but not in mice deficient in IL-10. Furthermore, we established that the acceleration of EAE in IL-10-deficient mice was associated with a decrease in IL-4 and an increase in IFN-gamma production in response to MOG antigen. These results strongly suggest that IL-10 plays a crucial role in the progression and recovery of autoimmune encephalomyelitis.
实验性自身免疫性脑脊髓炎（EAE）是一种中枢神经系统（CNS）的炎症性疾病，常被用作人类多发性硬化症（MS）的动物模型。该疾病由识别髓鞘自身抗原的自身反应性淋巴细胞介导。自身反应性淋巴细胞在中枢神经系统引发自身免疫炎症，导致脱髓鞘和神经功能丧失。尽管自身免疫性脑脊髓炎可导致不可逆的神经组织损伤和动物死亡，但EAE通常具有自发疾病恢复或缓解的特征。目前尚不清楚EAE的进展是如何调节的，也不清楚在动物体内髓鞘特异性淋巴细胞和髓鞘自身抗原仍然存在的情况下，中枢神经系统中的自身免疫炎症是如何消退的。长期以来，细胞因子，尤其是TH2型细胞因子，被认为在调节EAE中发挥作用。然而，使用重组细胞因子或细胞因子中和抗体的实验产生了相互矛盾的结果。为了确定白细胞介素（IL）-4和IL-10在实验性自身免疫性脑脊髓炎中的作用，我们研究了IL-4或IL-10缺陷的小鼠。我们发现，用髓鞘少突胶质细胞糖蛋白（MOG）免疫后，IL-10缺陷而非IL-4缺陷的小鼠EAE加速。重要的是，正常小鼠和IL-4缺陷小鼠的EAE可自发恢复，但IL-10缺陷小鼠则不能。此外，我们证实IL-10缺陷小鼠中EAE的加速与对MOG抗原反应时IL-4的减少和IFN-γ产生的增加有关。这些结果强烈表明，IL-10在自身免疫性脑脊髓炎的进展和恢复中起关键作用。
