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目的探讨IL-17对髓鞘碱性蛋白(MBP)68-86诱导鼻黏膜免疫耐受治疗实验性自身免疫性脑脊髓炎(EAE)的影响。方法将大鼠分为5组,分别经鼻黏膜滴注PBS、MBP68-86、MBP68-86+IL-17(0.01μg/d)、MBP68-86+IL-17(0.05μg/d)和MBP68-86+IL-17(0.1μg/d)诱导其发生免疫耐受,并在此基础上建立EAE动物模型,观察各组大鼠发病情况;通过3H掺入试验检测特异性抗原MBP68-86多肽诱导T淋巴细胞增殖活性;HE染色观察脊髓淋巴细胞浸润情况,免疫组化方法检测脊髓中单位面积IL-17+细胞数。结果PBS组和IL-170.1μg/d组与MBP组相比,大鼠免疫后出现进食减少、体重减轻、尾瘫、后肢瘫痪等临床症状,IL-170.01μg/d组和0.05μg/d组大鼠临床症状较轻或无症状。淋巴细胞增殖试验结果显示,PBS组和IL-170.1μg/d组与MBP组相比,特异性淋巴细胞增殖反应显著增高,IL-170.01μg/d组和0.05μg/d组与MBP组相比,差异无显著意义,与IL-170.1μg/d组相比差异有显著意义;PBS组、IL-170.1μg/d组与MBP组、IL-170.01μg/d组和0.05μg/d组相比,脊髓切片中淋巴细胞浸润面积较大且细胞数量较多,IL-17+细胞数也显著增多。结论MBP68-86特异性肽段可诱导EAE免疫耐受的形成,预防EAE的发生;鼻黏膜给予IL-17可以打破MBP诱导的特异性免疫耐受,且存在剂量依赖性。
Objective To investigate the effect of IL-17 on the immunosuppression of nasal mucosa induced by myelin basic protein (MBP) 68-86 in experimental autoimmune encephalomyelitis (EAE). Methods The rats were divided into 5 groups: PBS, MBP68-86, MBP68-86 + IL-17 (0.01μg / d), MBP68-86 + IL-17 -86 + IL-17 (0.1μg / d) induced immune tolerance, and on this basis, EAE animal model was established to observe the incidence of rats in each group; 3H-specific incorporation assay was used to detect the specific antigen MBP68-86 polypeptide The proliferation of T lymphocytes was induced. HE staining was used to observe the infiltration of lymphocytes in the spinal cord. The number of IL-17 + cells in the spinal cord was detected by immunohistochemistry. Results Compared with MBP group, the clinical symptoms such as decreased diet, weight loss, paralysis and hindlimb paralysis were observed in PBS group and IL-170.1μg / d group compared with MBP group. IL-170.01μg / d group and 0.05μg / d group The clinical symptoms of rats are light or asymptomatic. The results of lymphocyte proliferation test showed that the specific lymphocyte proliferation reaction was significantly increased in PBS group and IL-170.1μg / d group compared with MBP group, compared with MBP group in IL-170.01μg / d group and 0.05μg / d group , There was no significant difference between the two groups (P> 0.05). Compared with IL-170.1μg / d group, there was significant difference between PBS group, IL-170.1μg / d group and MBP group, IL-170.01μg / d group and 0.05μg / d group , Spinal cord sections of lymphocyte infiltration area larger and more cells, IL-17 + cell number also significantly increased. Conclusion MBP68-86 specific peptide can induce the formation of EAE immune tolerance and prevent the occurrence of EAE. Nasal mucosa administration of IL-17 can break the specific immune tolerance induced by MBP in a dose-dependent manner.