Foxp3-expressing CD4+T Cells Under the Control of IFN-γ Promoter Prevent Diabetes in NOD Mice.
Foxp3-expressing CD4+T Cells Under the Control of IFN-γ Promoter Prevent Diabetes in NOD Mice.
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DOI：
10.1038/sj.mt.6300208
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发表时间：
2007-08
期刊：
影响因子：
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通讯作者：
R. Wang;G. Han;Jianan Wang;Lun Song;Guojiang Chen;R. Xu;Ming Yu;J. Qian;B. Shen;Yan Li
中科院分区：
文献类型：
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作者：
R. Wang;G. Han;Jianan Wang;Lun Song;Guojiang Chen;R. Xu;Ming Yu;J. Qian;B. Shen;Yan Li
Foxp3-transduced CD4+T-cells have been used for treating autoimmune diseases such as type I diabetes. However, while suppressing the activity of pathogenic T cells, they could suppress the activity of bystander T cells as well. Therefore more specific strategies need to be developed. We designed and tested a new strategy that involves converting pathogenic CD4+Th1 cells into regulatory T-cells by lentiviral transduction with Foxp3 under the control of interferon-γ(IFN-γ) promoter (IγP-Foxp3). After transduction under the IγP control, Foxp3 expression in diabetic CD4+Th1 cells was favored. IγP-Foxp3-transduced CD4+T cells were anergicin vitroto stimulation by antigen. The process of IγP-Foxp3-transduced CD4+T cells differentiating into Treg cells and Treg cells losing their phenotype and functions has the effect of significantly suppressing incidence and onset of diabetes and autoantigen-specific T cell response, while increasing/maintaining endogenous Tregs in nonobese diabetic (NOD) mice recipients. In this manner, CD4+T cells of greater specificity were developed by transducing pathogenic CD4+Th1 cells with Foxp3 under the control of IγP, in order to prevent diabetes in NOD mice. The findings of this study provide a basis for more reasonable regulatory T cells (Tregs)-based therapy, with autoimmunity being suppressed through indirect means known as "infectious tolerance".
