We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Foxp3-expressing CD4<sup>+</sup>T Cells Under the Control of IFN-γ Promoter Prevent Diabetes in NOD Mice.
- Authors
Renxi Wang; Gencheng Han; Jianan Wang; Lun Song; Guojiang Chen; Ruonan Xu; Ming Yu; Jiahua Qian; Beifen Shen; Yan Li
- Abstract
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 anergic in vitro to 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”.Molecular Therapy (2007) 15 8, 1551–1557. doi:10.1038/sj.mt.6300208
- Publication
Molecular Therapy, 2007, Vol 15, Issue 8, p1551
- ISSN
1525-0016
- Publication type
Academic Journal
- DOI
10.1038/sj.mt.6300208