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

Jian Gu, Ling Lu, Maogen Chen, Lili Xu, Qin Lan, Qiang Li, Zhongmin Liu, Guihua Chen, Ping Wang, Xuehao Wang, David Brand, Nancy Olsen, Song Guo Zheng

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24 Scopus citations

Abstract

The use of TGF-β-induced CD4+Foxp3+T cells (induced regulatory T cells [iTregs]) is an important prevention and treatment strategy in autoimmune diseases and other disorders. However, the potential use of iTregs as a treatment modality for acute graftversus- host disease (aGVHD) has not been realized because they may be unstable and less suppressive in this disease.We restudied the ability of iTregs to prevent and treat aGVHD in two mouse models. Our results showed that, as long as an appropriate iTreggeneration protocol is used, these iTregs consistently displayed a potent ability to control aGVHD development and reduce mortality in the aGVHD 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 aGVHD. Therefore, we conclude that as long as the correct methods for generating iTregs are used, they can prevent and even treat aGVHD.

Original languageEnglish (US)
Pages (from-to)3388-3397
Number of pages10
JournalJournal of Immunology
Volume193
Issue number7
DOIs
StatePublished - Oct 1 2014

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Gu, J., Lu, L., Chen, M., Xu, L., Lan, Q., Li, Q., Liu, Z., Chen, G., Wang, P., Wang, X., Brand, D., Olsen, N., & Zheng, S. G. (2014). TGF-β-Induced CD4+Foxp3+T cells attenuate acute graft-versus-host disease by suppressing expansion and killing of effector CD8+cells. Journal of Immunology, 193(7), 3388-3397. https://doi.org/10.4049/jimmunol.1400207