FOXP3型
自身免疫
免疫学
白细胞介素2受体
CD40
生物
细胞毒性T细胞
白细胞介素21
抗体
调节性T细胞
CD8型
调节性B细胞
过继性细胞移植
T细胞
免疫系统
体外
B细胞
生物化学
作者
Karin Loser,Wiebke Hansen,Jenny Apelt,Sandra Balkow,Jan Buer,Stefan Beissert
出处
期刊:Gene Therapy
[Springer Nature]
日期:2005-06-16
卷期号:12 (17): 1294-1304
被引量:83
标识
DOI:10.1038/sj.gt.3302567
摘要
Regulatory T cells are promising candidates for the modulation of inflammation and autoimmunity. To generate regulatory T cells in vitro, we have infected naïve CD4+CD25- T cells with a retrovirus encoding the transcription factor Foxp3. Foxp3-infected T cells are similar to naturally occurring regulatory T cells as evidenced by surface marker expression and function. To investigate the effects of Foxp3-infected T cells on contact hypersensitivity (CHS) responses, sensitized mice were injected with Foxp3- or control virus-infected T cells. Only injection of Foxp3-infected T cells into sensitized mice significantly inhibited CHS compared to controls, indicating that Foxp3-infected T cells are suppressive in vivo. These findings prompted treatment of autoimmune-prone CD40L transgenic (tg) mice, which develop a severe systemic autoimmune disease including autoreactive T cells and autoantibodies, with Foxp3-infected T cells. Interestingly, injections of Foxp3-infected T cells into CD40L tg mice inhibited the ongoing development of autoimmune dermatitis and activation of cytotoxic CD8+ T cells. Strikingly, treatment with Foxp3-infected T cells reduced serum concentrations of antinuclear antibodies in CD40L tg mice, which was paralleled with reduced renal immunoglobulin depositions and increased kidney function. Together, these findings indicate that newly in vitro-generated regulatory T cells can be successfully used to treat inflammatory and ongoing autoimmune disorders.
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