Shi F D, Zhang G X, Bai X F, Van der Meide P H, Link H
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Clin Exp Immunol. 1997 Jun;108(3):523-8. doi: 10.1046/j.1365-2249.1997.3881284.x.
Age-related alterations in the immune system, including changes in lymphocyte subset composition, result in changes of cytokine patterns and might thereby influence the incidence and severity of autoimmune diseases. To investigate the age-related resistance to EAMG, an animal model for human MG, young (4-week-old) and adult (8-10-week-old) female Lewis rats were immunized with Torpedo acetylcholine receptor (AChR) and Freund's complete adjuvant (FCA). Adult Lewis rats showed severe weight loss and progressive muscular weakness after immunization, while young rats developed minor clinical signs of EAMG after a prolonged interval post-immunization. By comparison with adult rats, the young had lower AChR-specific T and B cells responses, and less muscle AChR loss. In situ hybridization performed on mononuclear cells (MNC) from lymph nodes revealed that young rats had lower levels of AChR-specific IFN-gamma, IL-4 and IL-10 mRNA-expressing cells compared with adult rats. Since IFN-gamma, IL-4 and IL-10 promote the development of EAMG, the low expression of these cytokines might contribute to EAMG resistance in young Lewis rats.
免疫系统中与年龄相关的改变,包括淋巴细胞亚群组成的变化,会导致细胞因子模式的改变,进而可能影响自身免疫性疾病的发病率和严重程度。为了研究对人类重症肌无力的动物模型实验性自身免疫性重症肌无力(EAMG)的年龄相关抵抗力,将年轻(4周龄)和成年(8 - 10周龄)雌性Lewis大鼠用鱼雷乙酰胆碱受体(AChR)和弗氏完全佐剂(FCA)进行免疫。成年Lewis大鼠免疫后出现严重体重减轻和进行性肌肉无力,而年轻大鼠在免疫后较长时间间隔才出现轻微的EAMG临床症状。与成年大鼠相比,年轻大鼠的AChR特异性T和B细胞反应较低,肌肉AChR损失较少。对来自淋巴结的单核细胞(MNC)进行原位杂交显示,与成年大鼠相比,年轻大鼠中表达AChR特异性干扰素 - γ(IFN - γ)、白细胞介素 - 4(IL - 4)和白细胞介素 - 10(IL - 10)mRNA的细胞水平较低。由于IFN - γ、IL - 4和IL - 10促进EAMG的发展,这些细胞因子的低表达可能有助于年轻Lewis大鼠对EAMG产生抵抗力。