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

TitleInhibition of accelerated rejection mediated by alloreactive CD4⁺ memory T cells and prolonged allograft survival by arsenic trioxide.
Publication TypeJournal Article
Year of Publication2013
AuthorsYan G, Xi Y, Xu S, Lin Y, Chen J, Dai H, Xia J, Li C, Li Q, Li Z, Qi Z
JournalImmunological investigations
Volume42
Issue5
Pagination438-54
Date Published2013
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.

DOI10.3109/08820139.2013.801986
Alternate JournalImmunol. Invest.