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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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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Graft vs Host Disease
T-Lymphocytes
Granzymes
Animal Disease Models
Regulatory T-Lymphocytes
Autoimmune Diseases
Cytokines
Mortality

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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. / TGF-β-Induced CD4+Foxp3+T cells attenuate acute graft-versus-host disease by suppressing expansion and killing of effector CD8+cells. In: Journal of Immunology. 2014 ; Vol. 193, No. 7. pp. 3388-3397.
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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.",
author = "Jian Gu and Ling Lu and Maogen Chen and Lili Xu and Qin Lan and Qiang Li and Zhongmin Liu and Guihua Chen and Ping Wang and Xuehao Wang and David Brand and Nancy Olsen and Zheng, {Song Guo}",
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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, SG 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, vol. 193, no. 7, pp. 3388-3397. https://doi.org/10.4049/jimmunol.1400207

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

In: Journal of Immunology, Vol. 193, No. 7, 01.10.2014, p. 3388-3397.

Research output: Contribution to journalArticle

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AU - Gu, Jian

AU - Lu, Ling

AU - Chen, Maogen

AU - Xu, Lili

AU - Lan, Qin

AU - Li, Qiang

AU - Liu, Zhongmin

AU - Chen, Guihua

AU - Wang, Ping

AU - Wang, Xuehao

AU - Brand, David

AU - Olsen, Nancy

AU - Zheng, Song Guo

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

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