Hoshioka A, Katsuki T, Saito K, Shimojo N, Niimi H, Kohno Y, Tarutani O
Department of Pediatrics, Chiba University School of Medicine.
Arerugi. 1992 Jan;41(1):65-72.
Thyroglobulin (Tg) is one of the major thyroid autoantigens involved in autoimmune thyroiditis. The immune response of mice to Tg is genetically controlled by H-2-linked genes. To elucidate the regulation mechanism of autoimmune response to Tg in low responder mice, we studied the proliferative response of lymph node cells (LNC) to mouse Tg (MTg) and enzyme-digested MTg fragments. MTg was treated with Staphylococcus aureus V8 protease followed by separation of the fragments into 6 fractions (Fr1-Fr6: 264,000-17,000) by high performance liquid chromatography (HPLC), LNC from MTg immunized CBA/N (H-2k) mice, a high responder strain, proliferated in response to MTg and all fractions (Fr1-Fr6) of MTg fragments in vitro. In contrast, LNC from MTg immunized BALB/c (H-2d) and B10 (H-2b) mice, low responder strains, did not respond to native Tg but responded well to some smaller Tg fractions (Fr3, 4, 5). In addition, when BALB/c mice were immunized with MTg Fr4 with a molecular weight of 63,000, LNC from BALB/c mice proliferated in response to MTg as well as MTg Fr4. These findings suggest that T cells which are capable of responding to Tg do exist even in low responder mice and that the activation of these autoreactive T cells is suppressed by a regulatory cell subpopulation in low responder mice.
甲状腺球蛋白(Tg)是参与自身免疫性甲状腺炎的主要甲状腺自身抗原之一。小鼠对Tg的免疫反应受H - 2连锁基因的遗传控制。为了阐明低反应性小鼠对Tg自身免疫反应的调节机制,我们研究了淋巴结细胞(LNC)对小鼠Tg(MTg)和酶消化的MTg片段的增殖反应。用金黄色葡萄球菌V8蛋白酶处理MTg,然后通过高效液相色谱(HPLC)将片段分离成6个组分(Fr1 - Fr6:264,000 - 17,000),来自MTg免疫的CBA/N(H - 2k)小鼠(高反应性品系)的LNC在体外对MTg和MTg片段的所有组分(Fr1 - Fr6)都有增殖反应。相比之下,来自MTg免疫的BALB/c(H - 2d)和B10(H - 2b)小鼠(低反应性品系)的LNC对天然Tg无反应,但对一些较小的Tg组分(Fr3、4、5)反应良好。此外,当用分子量为63,000的MTg Fr4免疫BALB/c小鼠时,来自BALB/c小鼠的LNC对MTg以及MTg Fr4都有增殖反应。这些发现表明,即使在低反应性小鼠中也存在能够对Tg作出反应的T细胞,并且这些自身反应性T细胞的激活在低反应性小鼠中被一个调节性细胞亚群所抑制。