Effects of natural or synthetic microbial adjuvants on induction of autoimmune thyroiditis.
Effects of natural or synthetic microbial adjuvants on induction of autoimmune thyroiditis.
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天然或合成微生物佐剂对诱导自身免疫性甲状腺炎的影响。
DOI：
10.1128/iai.49.1.40-45.1985
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发表时间：
1985
影响因子：
3.1
通讯作者：
Chedid,L
中科院分区：
文献类型：
--
作者：
Kong,YC;Audibert,F;Giraldo,AA;Rose,NR;Chedid,L
比较了微生物来源的天然和合成佐剂增强自身抗原小鼠甲状腺球蛋白（MTg）诱导实验性自身免疫性甲状腺炎（EAT）的能力。无论使用的免疫调节剂，严重的甲状腺炎只观察到在EAT敏感株的k单倍型，而不是在EAT耐药株的d单倍型。与酚提取的脂多糖（一种用于增强EAT诱导的有效佐剂）相比，邻苯二甲酰取代的解毒脂多糖即使在15至50倍的剂量下也仅导致低抗小鼠甲状腺球蛋白滴度和轻度甲状腺浸润。合成佐剂N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺（MDP）及其三种类似物，N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺-L-丙氨酰-D-甘油霉菌酸酯（MDP-L-Ala-Glyc-Myc）、N-乙酰胞壁酰-L-丙氨酰-D-谷氨酰-（癸基）甲酯[MDP（癸基）甲基]和N-乙酰胞壁酰-L-丙氨酰-D-谷氨酰胺-α正丁酯[MDP-（Gln）-OnBu]（命名为Murabutide），在不完全弗氏佐剂或盐水中进行测试。在不完全弗氏佐剂中，MDP-L-Ala-Glyc-Myc在诱导EAT方面是无效的，Murabutide诱导非常轻微的参与，并且MDP和更重要的是，MDP（癸基）甲基是有活性的，但程度低于CFA。当使用生理盐水时，仅在一个实验中在少数MDP处理的动物中观察到低水平的甲状腺浸润，而当使用Murabutide时未观察到病变。
Natural and synthetic adjuvants of microbial origin were compared for their capacity to potentiate the induction of experimental autoimmune thyroiditis (EAT) with the autoantigen mouse thyroglobulin (MTg). Regardless of the immunomodulator used, severe thyroiditis was observed only in EAT-susceptible strains of the k haplotype and not in EAT-resistant strains of the d haplotype. Compared to phenol-extracted lipopolysaccharide, a potent adjuvant for enhancing EAT induction, phthalyl-substituted, detoxified lipopolysaccharide, even at doses 15- to 50-fold greater, led to only low anti-mouse thyroglobulin titers and mild thyroid infiltration. The synthetic adjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and three of its analogs, N-acetylmuramyl-L-alanyl-D-isoglutamine-L-alanyl-D-glycerol mycolate (MDP-L-Ala-Glyc-Myc), N-acetylmuramyl-L-alanyl-D-glutamyl-(decyl)methyl ester [MDP(decyl)methyl], and N-acetylmuramyl-L-alanyl-D-glutamine-alpha n-butyl ester [MDP-(Gln)-OnBu], designated murabutide, were tested in incomplete Freund adjuvant or in saline. In incomplete Freund adjuvant, MDP-L-Ala-Glyc-Myc was inefficient in inducing EAT, murabutide induced very mild involvement, and MDP and, more so, MDP(decyl)methyl were active but to a lesser degree than CFA. When saline was used, low levels of thyroid infiltration were observed in a few of the MDP-treated animals in only one experiment, whereas no lesions were observed when murabutide was used.