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Mol Ther. 2007 Aug;15(8):1551-7. Epub 2007 May 29.

Foxp3-expressing CD4(+)T cells under the control of INF-gamma promoter prevent diabetes in NOD mice.

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  • 1Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.


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-gamma (IFN-gamma) promoter (IgammaP-Foxp3). After transduction under the IgammaP control, Foxp3 expression in diabetic CD4(+)Th1 cells was favored. IgammaP-Foxp3-transduced CD4(+)T cells were anergic in vitro to stimulation by antigen. The process of IgammaP-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 IgammaP, 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".

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