Inhibition of accelerated rejection mediated by alloreactive CD4⁺ memory T cells and prolonged allograft survival by arsenic trioxide

Abstract

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.

• Arsenic trioxide
• CD4⁺ memory T cell
• heart transplantation

Acknowledgements

We thank Xiaohong Ma (School of Life Sciences, Xiamen University) for her assistance with the FCM analysis.

Declaration of interest

This research was supported by grants from the Natural Science Foundation of Fujian Province (No. 2011J01253) and the Major State Scientific Research Program of China (No. 2012CBA01303).

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Authorship

Guoliang Yan designed and performed the research and wrote the paper, Yanfeng Xi designed the research and performed heart transplantation

Shuangyue Xu, provided assistance of statistical analysis and modified the paper

Yingying Lin, performed cell isolation, MLR and qRT-PCR assays

Jibing Chen, conducted research and modified the paper

Helong Dai, performed skin transplantation and FCM analysis

Junjie Xia, revised the paper

Chun Li, performed hematoxylin-eosin staining

Qing Li, performed skin transplantation

Zhi Li, contributed supporting funds

Zhongquan Qi, contributed important reagents and supporting funds

All authors read and approved the final manuscript.