经鼻黏膜给予MBP68-86和87-99协同免疫预防Lewis大鼠EAE的实验研究  

Inhibiton of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides:synergistic effects of MBP68-86 and 87-99

作　　者：孙博[1] 杨硕[1] 彭海生[1] 乔慧[1] 曹京燕[1] 金连弘[1] 李呼伦[1,2] 

机构地区：[1]哈尔滨医科大学神经生物学教研室哈尔滨医科大学神经生物省高校重点实验室 [2]华中科技大学同济医学院附属医院神经内科,湖北武汉430000

出　　处：《细胞与分子免疫学杂志》2007年第2期106-109,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家"十五"科技攻关资助项目(2004BA754C);国家自然科学基金资助项目(30370508)

摘　　要：目的探讨鼻黏膜给予MBP68-86和87-99协同免疫预防Lewis大鼠实验性自身免疫性脑脊髓炎(EAE)的作用。方法合成3条不同的碱性髓鞘蛋白(MBP)多肽(MBP68-86、87-99和非致脑炎性肽段110-128),在用豚鼠MBP(gp-MBP)加弗氏完全佐剂免疫Lewis大鼠前的11、10、9、8和7d,经鼻黏膜分别给予MBP多肽,观察其对EAE的保护作用。结果致脑炎性肽段MBP68-86和87-99都有保护作用,其中MBP68-86的保护作用更强;而MBP110-128没有保护作用。鼻黏膜给予MBP68-86+87-99的混合物,在相对低的剂量可完全阻断gp-MBP引发的EAE。淋巴细胞增殖实验和IFN-γELISPOT检测显示,与鼻黏膜给予大鼠MBP110-128组相比,鼻黏膜给予大鼠MBP68-86+87-99可降低T细胞对于MBP的反应性,淋巴结单核细胞中表达IFN-γ和TNF-αmRNA的细胞数减少,而两组表达TGF-β及IL-4mRNA的淋巴细胞数都低。结论鼻黏膜给予致脑炎性MBP多肽能够导致抗原特异性T细胞耐受,对gp-MBP引发的EAE提供不完全的保护,MBP68-86和MBP87-99具有协同作用。鼻黏膜给予多肽引发的免疫耐受与非调节机制有关。AIM： To explore the synergistic effect of MBP68-86 and 87-99, on the inhibition of experimental autoimmune encephalomyelitis （EAE） in Lewis rat by nasal administration. METHODS： Three different MBP peptides （MBP68-86, 87-99, and the non-encephalitogenic peptide 110-128） were synthesized and administrated nasally to Lewis rat on day-11, -10, -9, -8 and -7 prior to immunization with the guinea pig MBP （gp-MBP） ＋ CFA, which was used to induce EAE. The protective effect on Lewis rat from EAE by the MBP peptides was evaluated. RESULTS： Protection was achieved with the encephalitogenic peptides MBP68-86 and 87-99, MBP68-86 being more potent, but not with MBP 110-128. Neither MBP68-86 nor 87-99 used alone conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage than being used alone. Rats tolerized with MBP68-86 ＋ 87-99 nasally showed decreased T cell responses to MBP, reflected by lymphocyte proliferation and IFN-γ ELISPOT assays. Rats tolerized with MBP68-86 ＋ 87-99 also had abrogated MBP-reactive IFN-γ and TNF-α mRNA expression in lymph node cells compared to rats receiving MBP110-128 nasally, while similar low levels of MBP-reactive TGF-β and IL-4 mRNA expressing cells were observed in the two groups. CONCLUSION： Nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP- induced EAE, and MBP 68-86 and 87-99 have synergistic effecs, Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.

关 键 词：鼻黏膜耐受 MBP68-86 MBP87-99 实验性自身免疫性脑脊髓炎 

分 类 号：R392.12[医药卫生—免疫学]