期刊
BLOOD ADVANCES
卷 3, 期 24, 页码 4187-4201出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/bloodadvances.2019000531
关键词
-
类别
资金
- National Institutes of Health, National Cancer Institute [R01 CA118116, R01 CA169116]
- National Institutes of Health, National Institute of Allergy and Infectious Diseases [AI118305]
- National Institutes of Health, National Heart, Lung, and Blood Institute [HL137373]
- SmartState Endowment in Cancer Stem Cell Biology and Therapy Program
- Flow Cytometry and Cell Sorting shared resource, Hollings Cancer Center, MUSC [P30 CA138313]
Adoptive transfer of induced regulatory T cells (iTregs) can ameliorate graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). CD4(+) iTregs can effectively prevent GVHD but impair the graft-versus-leukemia (GVL) effect, whereas CD8(+) iTregs preserve the GVL effect but have limited efficacy in GVHD control because of their instability under inflammatory conditions. Thus, we aimed to stabilize CD8(+) iTregs via treatment with vitamin C (Vit C) to improve their efficacy in controlling GVHD. We found that addition of Vit C significantly improved the stability of forkhead box P3 (Foxp3) expression in CD8(+) iTregs. Moreover, Vit C-treated CD8(+) iTregs exhibited high efficacy in attenuating acute and chronic GVHD. The mechanistic study revealed that addition of Vit C to CD8(+) iTreg culture markedly increased DNA demethylation in the conserved noncoding sequence 2 region and, hence, maintained higher Foxp3 expression levels compared with untreated controls. In acute GVHD, Vit C-treated CD8(+) iTregs were able to inhibit pathogenic T-cell expansion and differentiation while reducing thymus damage and B-cell activation in cGVHD. Importantly, in contrast to CD4(+) iTregs, Vit C-treated CD8(+) iTregs retained the ability to control tumor relapse. These results provide a strong rationale to use Vit C in the clinic to stabilize CD8(+) iTregs for the control of GVHD and preservation of GVL after allo-HCT.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据