Curative and protective effects of IL-10 in experimental autoimmune thyroiditis (EAT). Evidence for IL-10-enhanced cell death in EAT.
Curative and protective effects of IL-10 in experimental autoimmune thyroiditis (EAT). Evidence for IL-10-enhanced cell death in EAT.
复制标题
IL-10 对实验性自身免疫性甲状腺炎 (EAT) 的疗效和保护作用。
作者：
K. Mignon;O. Rott;M. Brazillet;J. Charreire
我们研究了rhIL-10在两种实验性自身免疫性甲状腺炎（EAT）模型中体内给药的影响：1）在注射佐剂乳化的mTg诱导的EAT中，和2）在过继转移mTg特异性T淋巴细胞诱导的EAT中。此外，我们试图评估IL-10在EAT中的保护和治疗潜力，通过在用mTg引发和激发时或仅在激发时施用rhIL-10。我们证明，脾细胞对mTg的增殖和细胞毒性反应显着降低体内rhIL-10治疗。细胞表面标志物研究显示，在早期或晚期EAT中，用rhIL-10处理的小鼠的CD 4+和CD 8+淋巴母细胞样脾细胞减少40 - 45%。在用高剂量rhIL-10处理的小鼠中，EAT的严重程度显著降低，而针对mTg的自身抗体水平没有改变。此外，当分析纯化的T淋巴细胞从rhIL-10治疗的动物，增加细胞经历凋亡细胞死亡变得明显，在rhIL-10治疗组，与对照组相比。这种IL-10介导的激活诱导的细胞死亡的增强严重依赖于rhIL-10的应用治疗剂量。因此，IL-10通过一种可能暗示IL-10介导的T淋巴细胞活化诱导的细胞死亡增强的机制对EAT的发展和病程发挥有益作用，这一发现要求在早期免疫治疗中考虑IL-10，同样也是已经建立的自身免疫性甲状腺炎。
We studied the effects of in vivo administration of rhIL-10 in two models of experimental autoimmune thyroiditis (EAT): 1)-in EAT induced by injection of mTg emulsified in adjuvant, and 2) in EAT induced by adoptive transfer of mTg-specific T lymphocytes. Furthermore, we tried to assess both the protective and curative potential of IL-10 in EAT, by administering rhIL-10 either at the time of priming and challenge with mTg, or only at the time of challenge. We demonstrated that proliferative and cytotoxic responses of splenic cells to mTg were markedly reduced by in vivo rhIL-10 treatment. Cell surface marker studies revealed a 40 to 45% reduction in CD4+ and in CD8+ lymphoblastoid spleen cells from mice treated with rhIL-10 either in the early or in the late EAT. The severity of EAT was significantly reduced in mice treated with high-dose rhIL-10, whereas levels of autoantibodies to mTg were not altered. Furthermore, when analyzing purified T lymphocytes from rhIL-10-treated animals, an increase of cells undergoing apoptotic cell death became evident in the rhIL-10 treated group, as compared with controls. This IL-10-mediated enhancement of activation-induced cell death critically depended on the applied therapeutic dose of rhIL-10. Thus, IL-10 exerts beneficial effects on the development and course of EAT through a mechanism that could imply an IL-10-mediated enhancement of activation-induced cell death in T lymphocytes, findings that call for considering IL-10 in the immunotherapy of early-phase and likewise of already established autoimmune thyroiditis.