Fredrikson S, Sun J B, Huang W X, Li B L, Olsson T, Link H
Department of Neurology, Karolinska Institutet, Huddinge Hospital, Stockholm, Sweden.
J Immunol. 1993 Aug 15;151(4):2217-24.
To analyze Ag-specific T cell autoimmunity in the newborn, umbilical cord blood cells of newborns were investigated by an immunospot assay for occurrence and numbers of cells secreting IFN-gamma after short-term culture in presence of myelin basic protein (MBP), proteolipid protein, myelin associated glycoprotein, nicotinic acetylcholine receptor and the synthetic MBP amino acid sequences 1-20, 63-88, and 110-128. These Ag were chosen because they represent putative targets for autoimmune attack in multiple sclerosis and myasthenia gravis. Surprisingly, numbers of T cells recognizing MBP, proteolipid protein, MBP peptides, and acetylcholine receptor were high in cord blood of newborns compared to peripheral blood of patients with neurologic diseases. No immunodominant T cell epitope could be discerned among the Ag included. The responses to purified protein derivate and PHA were lower among cord blood cells than peripheral blood cells of adults. Parallel enumeration of autoimmune T cells in cord blood and peripheral blood obtained from corresponding mothers at delivery, revealed that the high cell numbers in newborns were not a result of contamination from the mothers blood. The high numbers of T cells recognizing nervous system myelin proteins and acetylcholine receptor in cord blood could have importance for the mechanism and timing of tolerance induction, and also reflect excessive myelination and receptor maturation at birth.
为分析新生儿中抗原特异性T细胞自身免疫情况,采用免疫斑点试验对新生儿脐带血细胞进行研究,检测其在髓鞘碱性蛋白(MBP)、蛋白脂蛋白、髓鞘相关糖蛋白、烟碱型乙酰胆碱受体以及合成的MBP氨基酸序列1 - 20、63 - 88和110 - 128存在的情况下短期培养后分泌γ干扰素的细胞的出现情况和数量。选择这些抗原是因为它们代表了多发性硬化症和重症肌无力中自身免疫攻击的假定靶点。令人惊讶的是,与神经疾病患者的外周血相比,新生儿脐带血中识别MBP、蛋白脂蛋白、MBP肽和乙酰胆碱受体的T细胞数量较高。在所包含的抗原中未发现免疫显性T细胞表位。脐带血细胞对纯化蛋白衍生物和PHA的反应低于成人外周血细胞。对分娩时从相应母亲处获得的脐带血和外周血中的自身免疫性T细胞进行平行计数,结果显示新生儿中T细胞数量高并非母亲血液污染所致。脐带血中识别神经系统髓鞘蛋白和乙酰胆碱受体的T细胞数量较多,这可能对耐受性诱导的机制和时机具有重要意义,也反映了出生时过度的髓鞘形成和受体成熟。