Saegusa K, Ishimaru N, Haneji N, Yanagi K, Yoneda T, Saito I, Hayashi Y
Department of Pathology, Tokushima University School of Dentistry, 3 Kuramotocho, Tokushima 770, Japan.
Scand J Immunol. 2000 Sep;52(3):264-70. doi: 10.1046/j.1365-3083.2000.00777.x.
Neonatal exposure to autoantigen is believed to induce effective antigen-specific T-cell tolerance in experimental models of autoimmunity. We have identified 120 kDa alpha-fodrin autoantigen in an animal model for primary Sjögren's syndrome (SS), that has been determined as a candidate autoantigen in both an animal model and the patients with primary SS. We demonstrate here that neonatal injection of autoantigen induce relevant tolerance when treated with intravenous (i.v.) administration within 24 h after birth, but not with i.v. injection after the thymectomy or with intraperitoneal injection. Autoantigen-specific T-cell response was significantly reduced in mice induced neonatal tolerance, and the activation markers of splenic CD4+ T cells were down-regulated in mice treated with neonatal administration. Because we detected that neonatal i.v. injection of autoantigen prevented Th1 response, it is possible that the autoantigen administration within 24 h after birth induce regulatory T cells that had a protective effect against Th1-mediated autoimmune diseases. These results indicate that the prevention of the spontaneous anti-120 kDa alpha-fodrin response in vivo, by tolerization of the autoantigen-reactive T cells, blocked the development of autoimmune lesions in an animal model for primary SS.
在自身免疫性疾病的实验模型中，新生儿暴露于自身抗原被认为可诱导有效的抗原特异性T细胞耐受。我们在原发性干燥综合征（SS）的动物模型中鉴定出了120 kDa的α-血影蛋白自身抗原，该抗原在动物模型和原发性SS患者中均被确定为候选自身抗原。我们在此证明，在出生后24小时内通过静脉内（i.v.）给药进行新生儿自身抗原注射可诱导相关耐受，但胸腺切除术后进行静脉注射或腹腔注射则不能诱导耐受。在诱导了新生儿耐受的小鼠中，自身抗原特异性T细胞反应显著降低，并且在接受新生儿给药治疗的小鼠中，脾脏CD4 + T细胞的激活标志物下调。因为我们检测到新生儿静脉注射自身抗原可预防Th1反应，所以有可能在出生后24小时内给予自身抗原可诱导调节性T细胞，这些调节性T细胞对Th1介导的自身免疫性疾病具有保护作用。这些结果表明，通过使自身抗原反应性T细胞耐受来预防体内自发的抗120 kDaα-血影蛋白反应，可阻断原发性SS动物模型中自身免疫性病变的发展。
