Basic Medical Department of Medical College, Xiamen University, Xiamen City, Fujian Province, P. R. China.
Immunol Invest. 2013;42(5):438-54. doi: 10.3109/08820139.2013.801986.
The aim of this study was to evaluate and determine the potential mechanisms of As₂O₃ in accelerated rejection mediated by alloreactive CD4⁺ memory T cells. Vascularized heterotopic cardiac transplantation from C57BL/6 mice to nude mice (pre-transferred CD4⁺ memory T cells) was performed on Day 0, and As₂O₃ was administered to recipient mice from Day 0 to 10. As a result, As₂O₃ could reduce the proliferation of allo-primed CD4⁺ memory T cells in vitro in MLR and the baseline rate of proliferation was restored by the addition of exogenous IL-2. In vivo, compared with the control[+] group, the mean survival time of cardiac allografts in the As₂O₃ group was prolonged from 5.8 ± 0.7 to 14.2 ± 2.5 days. Five days after transplantation, the relative gene expression of IL-2, IFN-γ and Foxp3 was reduced in the grafts by As₂O₃ treatment, but the expression of IL-10 and TGF-β was increased. Correspondingly, the proportions of CD4⁺ T cells, CD4⁺ memory T cells and regulatory T cells (Tregs), both in recipient spleens and lymph nodes, were lowered. These results indicate the potential of As2O3 as a novel immunosuppressant targeting CD4⁺ memory T cells.
本研究旨在评估和确定三氧化二砷（As₂O₃）在同种反应性 CD4⁺记忆 T 细胞介导的加速排斥反应中的潜在机制。于第 0 天对 C57BL/6 小鼠到裸鼠的血管化异位心脏移植（预先转移 CD4⁺记忆 T 细胞）进行操作，并于第 0 天至第 10 天对受者小鼠给予 As₂O₃。结果表明，As₂O₃可降低体外 MLR 中同种致敏的 CD4⁺记忆 T 细胞的增殖，且添加外源性 IL-2 可恢复其基础增殖率。在体内，与对照组相比，As₂O₃组的心脏移植物平均存活时间从 5.8±0.7 天延长至 14.2±2.5 天。移植后 5 天，As₂O₃处理可降低移植物中 IL-2、IFN-γ 和 Foxp3 的相对基因表达，但增加 IL-10 和 TGF-β的表达。相应地，受体脾脏和淋巴结中 CD4⁺T 细胞、CD4⁺记忆 T 细胞和调节性 T 细胞（Tregs）的比例均降低。这些结果表明 As₂O₃作为一种针对 CD4⁺记忆 T 细胞的新型免疫抑制剂具有潜力。
