title: TGF-β-induced CD4+Foxp3+ T cells attenuate acute graft-versus-host disease by suppressing expansion and killing of effector CD8+ cells.
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 graft-versus-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 iTreg-generation 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.
authors.affiliation: Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China; Division of Rheumatology, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033; Clinical Immunology Section, Third Affiliated Hospital at Sun Yat-Sen University, Guangzhou 510630, China;
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China;
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Organ Transplant Center, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China;
authors.forename: Maogen
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Molecular Biosciences, Stockholm University, SE-10691 Stockholm, Sweden;
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.affiliation: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; and.
authors.forename: Qin
authors.initials: Q
authors.lastname: Lan
authors.affiliation: Organ Transplant Center, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China;
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; and.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Clinical Immunology Section, Third Affiliated Hospital at Sun Yat-Sen University, Guangzhou 510630, China;
authors.forename: Guihua
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China; szheng1@hmc.psu.edu wuwpzhy@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Liver Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China;
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Research Service, Veterans Affairs Medical Center, Memphis, TN 38104.
authors.forename: David
authors.initials: D
authors.lastname: Brand
authors.affiliation: Division of Rheumatology, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033;
authors.forename: Nancy
authors.initials: N
authors.lastname: Olsen
authors.affiliation: Division of Rheumatology, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033; Clinical Immunology Section, Third Affiliated Hospital at Sun Yat-Sen University, Guangzhou 510630, China; szheng1@hmc.psu.edu wuwpzhy@163.com.
authors.forename: Song Guo
authors.initials: SG
authors.lastname: Zheng
mesh_terms: D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D053804:Granzymes / Q000276:immunology; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta; D053804:Granzymes; C509214:Gzmb protein, mouse