未成熟髓源树突状细胞负载P2 58-73肽段诱导免疫耐受对实验性自身免疫性神经炎的预防作用  

Preventive effect of immune tolerance induced by immature myeloid dendritic cell loading P2 58-73 peptide in experimental autoimmune neuritis

作　　者：胡珏[1] 张海萍[2] 肖波[2] 李庆华[2] 张勇[2] 周红轮[1] 杨欢[2] 

机构地区：[1]长沙市中心医院神经内科,410000 [2]中南大学湘雅医院神经内科

出　　处：《临床神经病学杂志》2009年第4期293-296,共4页Journal of Clinical Neurology

基　　金：国家自然科学基金资助项目(30570639);湖南省卫生厅课题(B2006-199)

摘　　要：目的观察未成熟髓源树突状细胞(iMDC)负载P258-73肽段诱导免疫耐受对实验性自身免疫性神经炎(EAN)的预防作用,以及对干扰素-γ(IFN-γ)、白介素-33(IL-33)mRNA表达的影响。方法(1)P258-73aa与iMDC共培养。(2)21只Lewis大鼠随机分为EAN组(A组)、iMDC组(B组)和P258-73aa-iMDC组(C组),并分别于皮下注射磷酸盐缓冲液(PBS)、iMDC及P258-73aa-iMDC;7d后,各组均给予P253-78aa和完全弗氏佐剂(CFA)进行免疫,诱发EAN。观察各组发病情况并作临床评分至免疫后16d(发病高峰期)。(3)采用3H-TdR掺入法检测淋巴细胞增殖反应;RT-PCR检测大鼠坐骨神经、脾脏和淋巴结中IL-33、IFN-γmRNA的表达。结果(1)发病高峰期,A组、B组、C组的临床评分为(7.4±1.9)分、(5.2±1.6)分和(3.4±0.9)分,各组间比较差异有统计学意义(均P<0.01)。(2)A组、B组、C组抗原特异性淋巴细胞增殖反应依次明显降低(均P<0.01)。(3)A组、B组、C组坐骨神经、脾脏和淋巴结中IFN-γmRNA表达水平依次明显降低,IL-33mRNA表达依次明显增高(P<0.05～0.01)。结论P258-73aa-iMDC能减轻EAN的发病;其可能通过抑制抗原特异性淋巴细胞增殖、降低IFN-γ分泌、上调IL-33的分泌诱导免疫耐受。Objective To observe the preventive effect of immune tolerance induced by immature myeloid dendritic cell （iMDC） loading P2 58-73 peptide （P2 58-73aa-iMDC） in experimental autoimmune neuritis （EAN） , and the effect on the expression of IFN-γ, and IL-33 mRNA. Methods （ 1 ） The iMDC were cultured in vitro for loading P2 58-73aa. （2） 21 adult female Lewis rats were randomly divided into the EAN （A）group, iMDC （B）group and P2 58-73aa -iMDC（C） group, and subcutaneously injected PBS, iMDC and P2 58-73aa-iMDC respectively. After 7 d, all the rats were immunized with P2 53-78aa and complete freunds adjuvant （CFA） to inducing EAN. Then , the situation of onset were observed and clinical score were evaluated till 16 d （the crest-time of onset ） after immunization. （3） The lymphocyte proliferative response were assayed by 3 H-TdR incorporation. The expression of IL-33, IFN-γ mRNA in sciatic nerves, spleen and lymph node were detected by RT-PCR. Results （ 1 ） In the cresttime of onset, the clinical scores in groups A,B and C were （7.4 ± 1.9）, （5.2 ± 1.6） and （3.4 ±0.9） respectively. There were significant differences between each two groups （ all P 〈 0. 01 ）. （ 2 ） The antigen specific lymphocyte proliferation in groups A, B, C were significantly decreased in proper order（ all P 〈 0. 01 ）. （ 3 ） In groups A, B and C, the expression levels of IFN-γ mRNA in sciatic nerves, spleen and lymph node were significantly reduced in proper order, while IL-33 mRNA were significantly increased in proper order （P〈 0. 05 -0. 01 ）. Conclusions P2 58-73aa-iMDC can ameliorate onset of EAN. The protective effect of it may be associated with the antigenic specific suppression of lymphocyte proliferation and reducing expression of IFN-γ,increasing the expression of IL-33 to induce immune tolerance.

关 键 词：实验性自身免疫性神经炎 未成熟髓源树突状细胞 免疫耐受 

分 类 号：R741[医药卫生—神经病学与精神病学]