Zheng Yan, Jost Monika, Gaughan John P, Class Reiner, Coyle Anthony J, Monestier Marc
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
J Immunol. 2005 Mar 1;174(5):3117-21. doi: 10.4049/jimmunol.174.5.3117.
After exposure to subtoxic doses of heavy metals such as mercury, H-2(s) mice develop an autoimmune syndrome consisting of the rapid production of IgG autoantibodies that are highly specific for nucleolar autoantigens and a polyclonal increase in serum IgG1 and IgE. In this study, we explore the role of one of the members of the CD28-B7 costimulation families, ICOS-B7 homologous protein (B7h), in the regulation of mercury-induced autoimmunity. The expression of ICOS on T cells was more enhanced in susceptible A.SW mice than in non-responsive C57BL/6 and DBA/2 mice after HgCl(2) treatment. Furthermore, in A.SW mice treated with HgCl(2), administration of a blocking anti-ICOS Ab effectively inhibited anti-nucleolar autoantibodies and total serum IgE production. Taken together, these results indicate that the ICOS-B7h costimulation pathway is required for this autoimmune syndrome and suggest that targeting this pathway might have therapeutic benefits for human autoimmune diseases.
在接触亚毒性剂量的重金属（如汞）后，H-2(s)小鼠会发展出一种自身免疫综合征，其特征包括快速产生对核仁自身抗原具有高度特异性的IgG自身抗体，以及血清IgG1和IgE的多克隆增加。在本研究中，我们探讨了CD28-B7共刺激家族成员之一的诱导共刺激分子配体（ICOS-B7同源蛋白，B7h）在汞诱导的自身免疫调节中的作用。在氯化汞（HgCl₂）处理后，易感性A.SW小鼠T细胞上ICOS的表达比无反应性的C57BL/6和DBA/2小鼠增强得更多。此外，在用HgCl₂处理的A.SW小鼠中，给予阻断性抗ICOS抗体可有效抑制抗核仁自身抗体和总血清IgE的产生。综上所述，这些结果表明ICOS-B7h共刺激途径是这种自身免疫综合征所必需的，并提示针对该途径可能对人类自身免疫性疾病具有治疗益处。
