T细胞定向迁移诱导实验性自身免疫性脑脊髓炎小鼠胸腺萎缩

Oriented T cell migration induces thymic atrophy in experimental autoimmune encephalomyelitis in mice

目的 初步探讨实验性自身免疫性脑脊髓炎（EAE）小鼠胸腺萎缩的机制.方法 髓鞘少突胶质细胞糖蛋白（MOG）免疫C57BL/6小鼠诱导EAE,卵清白蛋白（OVA）免疫的小鼠作为对照;不同时间点计数胸腺、脾脏、淋巴结细胞总数,检测脾脏中胸腺来源细胞及中枢神经系统（CNS）浸润细胞.结果 MOG肽成功诱导EAE动物模型,小鼠出现典型的肢体运动功能障碍,脊髓可见大量炎性细胞浸润;MOG和OVA免疫均诱导胸腺细胞增加,第5天达到高峰,随后逐渐下降;EAE发病后胸腺细胞迅速减少,发病高峰期几乎完全消失,胸腺严重萎缩;MOG和OVA免疫后脾脏和淋巴结细胞总数持续升高,新近胸腺来源的T细胞增加尤其明显;EAE发病后脾脏T细胞总数减少,CNS浸润淋巴细胞总数增加.结论 大量T细胞在胸腺发育成熟并释放到外周,进而定向迁移至CNS诱导EAE是胸腺萎缩的主要原因.

Objective To investigate the mechanisms of thymic atrophy in experimental autoimmune encephalomyelitis （EAE）.Methods EAE was induced in C57BL/6 mice.The mice immunized with OVA peptide were served as control.The amount of cells were determined in thymus,spleen and lymph nodes at different time points.Thymus-derived T cells in the spleen and infiltrating cells in central nervous system（CNS） were analyzed.Results EAE with typical motor system dysfunction and monocyte infiltration in CNS was induced by MOG peptide in CFA.The number of cells in the thymus was increased,and peaked at day 5,followed by a decrease when mice were immunized with OVA or MOG peptide.From the onset of the disease （day 10）,thymocytes reduced rapidly and completely lost in some cases with severe disease.After immunization,lymphocytes in spleen and dLNs,especially recently thymus-derived T cells,continuously increased prior to the onset of the disease.However,upon the mice have developed EAE,T cells in the spleen decreased rapidly,accompanied by a dramatic increase of the infiltrated lymphocytes in CNS.Conclusion Enhanced thymus T cell output and oriented T-cell migration to CNS contribute to thymic atrophy in EAE.