Mozes E, Zinger H, Kohn L D, Singer D S
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Immunol. 1998 Mar;18(2):106-13. doi: 10.1023/a:1023242732212.
(NZB x NZW)F1 mice spontaneously develop with age an autoimmune disease that resembles the human disease, systemic lupus erythematosus (SLE). The present study demonstrates that methimazole (MMI), an agent used in the treatment of autoimmune thyroid disease, is effective in mitigating the development of this SLE-like autoimmune disease in (NZB x NZW)F1 mice. MMI significantly reduces the incidence and severity of proteinuria and deposition of immune complexes in the kidney. Previous studies have demonstrated that development of an experimentally induced SLE, which was prevented by MMI treatment, depended on the expression of MHC class I molecules. We now report that class I levels on both T cells and B cells from old (NZB x NZW)F1 MHC class I are markedly elevated relative to those from young F1 mice. Furthermore, treatment of (NZB x NZW)F1 mice with MMI reduced MHC class I expression on their PBL concomitant with amelioration of disease, raising the possibility that class I molecules may play a role in the generation of spontaneous autoimmune disease in these mice.
（新西兰黑鼠×新西兰白鼠）F1代小鼠会随着年龄增长自发患上一种类似于人类系统性红斑狼疮（SLE）的自身免疫性疾病。本研究表明，用于治疗自身免疫性甲状腺疾病的药物甲巯咪唑（MMI），在减轻（新西兰黑鼠×新西兰白鼠）F1代小鼠这种类SLE自身免疫性疾病的发展方面是有效的。MMI显著降低了蛋白尿的发生率和严重程度以及肾脏中免疫复合物的沉积。先前的研究表明，实验性诱导的SLE的发展（MMI治疗可预防）依赖于MHC I类分子的表达。我们现在报告，与年轻F1代小鼠相比，老龄（新西兰黑鼠×新西兰白鼠）F1代小鼠的T细胞和B细胞上的I类水平显著升高。此外，用MMI治疗（新西兰黑鼠×新西兰白鼠）F1代小鼠可降低其外周血淋巴细胞上的MHC I类表达，同时改善疾病状况，这增加了I类分子可能在这些小鼠自发自身免疫性疾病的发生中起作用的可能性。
