title: Cytotoxic T Lymphocyte Antigen-4 Down-Regulates T Helper 1 Cells by Increasing Expression of Signal Transducer and Activator of Transcription 3 in Acute Graft-versus-Host Disease.
abstract: Numerous previous studies have suggested that cytotoxic T lymphocyte antigen-4 (CTLA-4) plays an important role in acute graft-versus-host disease (GVHD). How CTLA-4 acts in regulating acute GVHD remains unknown, however. In the present study, we found that, compared with healthy controls, CTLA-4 plasma and relative mRNA levels in patients with acute GVHD were initially decreased and then markedly elevated after 28 days of treatment. CTLA-4 levels were higher in patients with grade I-II acute GVHD compared with those with grade III-IV acute GVHD both before and after treatment. Up-regulation of CTLA-4 significantly increased the luciferase activity and degree of phosphorylation of signal transducer and activator of transcription 3 (STAT3). Meanwhile, T cell activation was significantly inhibited, and levels of IFN-γ, IL-17, and IL-22 decreased. These findings suggest that CTLA-4 might be involved in the pathogenesis of acute GVHD, and may down-regulate T helper 1 cells by increasing STAT3 expression in acute GVHD.
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Affiliated Huai'an First People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Zhong
authors.affiliation: Laboratory of Transplant Immunology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Laboratory of Transplant Immunology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Laboratory of Transplant Immunology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Wu
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sang
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yan
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Laboratory of Transplant Immunology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Zeng
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Laboratory of Transplant Immunology, Xuzhou Medical College, Xuzhou, Jiangsu, China. Electronic address: lihmd@163.com.
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D060908:CTLA-4 Antigen / Q000378:metabolism*; D005260:Female; D006086:Graft vs Host Disease / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; D050796:STAT3 Transcription Factor
keywords: Acute graft-versus-host disease; Cytotoxic T lymphocyte antigen 4; STAT3; T helper 1 cell