【摘要】 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。更多还原

【Abstract】 Objective To explore the effect of IL-17 on therapy of experimental autoimmune encephalomyelitis (EAE) by nasal immunotolerance induced with myelin basic protein(MBP) 68-86. Methods Lewis rats were divided into five groups and immunized with PBS, MBP68-86, MBP68-86 + IL-17 (0. 01 μg / d), MBP68-86 + IL-17 (0. 05 μg / d) and MBP68-86 + IL-17 (0. 1 μg / d) by intranasal drip respectively to induce immunotolerance, based on which the rat model of EAE was established and observed for morbidity. Determine the activity of MBP68-86 in inducing T lymphocyte proliferation by 3H incorporation test, the infiltration of lymphocytes in spinal cord by HE staining, and the number of IL-17-positive cells per unit area in spinal cord by immunohistochemical method. Results Clinical signs such as decreases of food intake and bodyweight as well as paralysis of tail and posterior limbs were observed in rats immunized with PBS and MBP68-86 + IL-17(0. 1 μg / d). However, mild or no clinical signs were observed in those immunized with MBP68-86, MBP68-86 + IL-17 (0. 01 μg / d) and MBP68-86 + IL-17 (0. 05 μg / d). The specific lymphocyte proliferation levels of rats immunized with PBS and MBP68-86+IL-17(0. 1 μg / d) were significantly higher than that with MBP68-86. The specific lymphocyte proliferation levels of rats immunized with MBP68-86 + IL-17 (0. 01 μg / d) and MBP68-86+IL-17 (0. 05 μg / d) showed no significant difference with that immunized with MBP68-86, while showed significant difference with that immunized with MBP68-86 + IL-17 (0. 1 μg / d). Compared with those immunized with MBP68-86, MBP68-86 + IL-17 (0. 01 μg / d) and MBP68-86 + IL-17 (0. 05 μg / d), the area of lymphocyte infiltration and the number of in spinal cord section of rats immunized with PBS and MBP68-86 + IL-17 (0. 1 μg / d) were large, and both the numbers of lymphocytes and IL-17-positive cells increased. Conclusion MBP68-86 specific peptide induced immunotolerance and prevented the occurrence of EAE. However, intranasal drip with IL-17 broke the induced specific immunotolerance in a dose-dependent mode.更多还原