TGF-β-induced CD4+Foxp3+ T cells attenuate acute graft-versus-host disease via suppressing expansion and killing of effector CD8+ cells

• Published in: The Journal of immunology (1950) 2014-08, Vol.193 (7), p.3388-3397
• Main Authors: Gu, Jian, Lu, Ling, Chen, Maogen, Xu, Lili, Lan, Qin, Li, Qiang, Liu, Zhongmin, Chen, Guihua, Wang, Ping, Wang, Xuehao, Brand, David, Olsen, Nancy, Zheng, Song Guo
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1400207

TGF-β-induced CD4 + Foxp3 + T cells (iTregs) have been identified as important prevention and treatment strategies for cell therapy in autoimmune diseases and other disorders. However, the potential use of iTregs as a treatment modality for acute graft- verse -host disease (GVHD) has not been realized because iTregs may be unstable and less suppressive in this disease. Here we restudied the ability of iTregs to prevent and treat acute GVHD in two different mouse models. Our results showed that so long as an appropriate iTreg-generation protocol is used, these iTregs consistently displayed a potent ability to control acute GVHD development and reduce mortality in the acute GVHD animal models. iTreg infusion markedly suppressed the engraftment of donor CD8 + cells and CD4 + cells, the expression of Granzyme A and B, the cytotoxic effect of donor CD8 + cells and the production of T cell cytokines in acute GVHD. We therefore conclude that so long as the right methods for generating iTreg cells have been employed, iTregs can indeed prevent and even treat acute GVHD.