Kong Y M, David C S, Lomo L C, Fuller B E, Motte R W, Giraldo A A
Department of Immunology and Microbiology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI 48201, USA.
Immunogenetics. 1997;46(4):312-7. doi: 10.1007/s002510050277.
Mouse experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis, is induced by immunizing with mouse thyroglobulin (MTg). To study the extent of H2A involvement in EAT, we introduced AaAb genes from susceptible k mice into resistant or intermediately susceptible strains which do not express H2E molecules. Thyroiditis was severe in resistant B10.M (H2(f)) mice carrying the double transgene AakAbk. Likewise, thyroid infiltration was significantly extended in intermediate B10.Q (H2(q)) mice with the same transgene. To examine the effect of H2E molecules in the presence of H2A-mediated susceptibility, we introduced an Eak transgene into E- B10.S mice to express the Ebetas molecule and observed significant reduction in EAT severity in B10.S(E+) mice. On the other hand, the presence of an Ebd transgene in B10.RQB3 (H2Aq) mice resulting in the expression of H2Ebetad molecules did not alter EAT susceptibility, suggesting a role for Eb gene polymorphism in protection against EAT. We have shown recently that the HLA-DRB1()0301 (DR3) transgene conferred EAT susceptibility to B10. M as well as class II-negative B10.Ab0 mice. However, we report here that the HLA-DQB1()0601 (DQ6b) transgene in B10.M or HLA-DQA1()0301/DQB1()0302 (DQ8) transgene in class II-negative Ab0 mice did not. These studies show the differential effects of class II molecules on EAT induction. Susceptibility can be determined when class II molecules from a single locus, H2A or HLA-DQ, are examined in transgenic mice, but the overall effect may depend upon the presence of both class II molecules H2A and H2E in mice and HLA-DQ and HLA-DR in humans.
小鼠实验性自身免疫性甲状腺炎（EAT）是桥本甲状腺炎的一种模型，通过用小鼠甲状腺球蛋白（MTg）免疫诱导产生。为了研究H2A在EAT中的参与程度，我们将来自易感k小鼠的AaAb基因导入不表达H2E分子的抗性或中度易感品系。携带双转基因AakAbk的抗性B10.M（H2(f)）小鼠发生严重的甲状腺炎。同样，具有相同转基因的中度易感B10.Q（H2(q)）小鼠的甲状腺浸润也显著扩展。为了研究在H2A介导的易感性存在时H2E分子的作用，我们将Eak转基因导入E - B10.S小鼠以表达Ebetas分子，并观察到B10.S(E+)小鼠的EAT严重程度显著降低。另一方面，B10.RQB3（H2Aq）小鼠中存在导致H2Ebetad分子表达的Ebd转基因并没有改变EAT易感性，这表明Eb基因多态性在预防EAT中起作用。我们最近表明，HLA - DRB1()0301（DR3）转基因使B10.M以及II类阴性B10.Ab0小鼠易患EAT。然而，我们在此报告，B10.M中的HLA - DQB1()0601（DQ6b）转基因或II类阴性Ab0小鼠中的HLA - DQA1()0301/DQB1()0302（DQ8）转基因并没有此作用。这些研究显示了II类分子对EAT诱导的不同影响。当在转基因小鼠中检查来自单个基因座H2A或HLA - DQ的II类分子时，可以确定易感性，但总体效果可能取决于小鼠中H2A和H2E这两种II类分子以及人类中HLA - DQ和HLA - DR的存在情况。
