Morris Gerald P, Chen Lieping, Kong Yi-chi M
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Cell Immunol. 2003 Nov;226(1):20-9. doi: 10.1016/j.cellimm.2003.11.002.
Experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis, is a T cell-mediated disease inducible with mouse thyroglobulin (mTg). Pretreatment with mTg, however, can induce CD4+ T cell-mediated tolerance to EAT. We demonstrate that CD4+CD25+ regulatory cells are critical for the tolerance induction, as in vivo depletion of CD25+ cells abrogated established tolerance, and CD4+CD25+ cells from tolerized mice suppressed mTg-responsive cells in vitro. Importantly, administration of an agonistic CD137 monoclonal antibody (mAb) inhibited tolerance development, and the mediation of established tolerance. CD137 mAb also inhibited the suppression of mTg-responsive cells by CD4+CD25+ cells in vitro. Signaling through CD137 likely resulted in enhancement of the responding inflammatory T cells, as anti-CD137 did not enable CD4+CD25+ T cells to proliferate in response to mTg in vitro.
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，是一种由小鼠甲状腺球蛋白（mTg）诱导的T细胞介导的疾病。然而，用mTg进行预处理可诱导CD4 + T细胞介导的对EAT的耐受性。我们证明，CD4 + CD25 +调节性细胞对于耐受性诱导至关重要，因为体内去除CD25 +细胞可消除已建立的耐受性，并且来自耐受小鼠的CD4 + CD25 +细胞在体外抑制mTg反应性细胞。重要的是，给予激动性CD137单克隆抗体（mAb）可抑制耐受性的发展以及已建立的耐受性的介导。CD137 mAb在体外也抑制了CD4 + CD25 +细胞对mTg反应性细胞的抑制作用。通过CD137发出的信号可能导致反应性炎症T细胞增强，因为抗CD137不能使CD4 + CD25 + T细胞在体外对mTg作出增殖反应。
