Cytotoxic T Lymphocyte Antigen-4 Down-Regulates T Helper 1 Cells by Increasing Expression of Signal Transducer and Activator of Transcription 3 in Acute.

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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 Feng Zhu, Xiao-Min Zhong, Jianlin Qiao, Qiong Liu, Hai-Ying Sun, Wei Chen, Kai Zhao, Qing-Yun Wu, Jiang Cao, Wei Sang, Zhi-Ling Yan, Ling-Yu Zeng, Zhen-Yu Li, Kai-Lin Xu Biology of Blood and Marrow Transplantation Volume 22, Issue 2, Pages 212-219 (February 2016) DOI: 10.1016/j.bbmt.2015.11.003 Copyright © 2016 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 (A) CTLA-4 mRNA expression in patients with acute GVHD identified by RT-PCR. (B) CTLA-4 protein levels in patients with acute GVHD measured by Western blot analysis, 1-5, five patients with acute GVHD; M, marker. Biology of Blood and Marrow Transplantation 2016 22, 212-219DOI: (10.1016/j.bbmt.2015.11.003) Copyright © 2016 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Expression of CTLA-4 in responders (R) with grade I-II and III-IV acute GVHD and healthy controls. (A) CTLA-4 expression in healthy controls and responders with acute GVHD before and after treatment measured by ELISA. (B) CTLA-4 expression in healthy controls and responders with acute GVHD before and after treatment measured by q-PCR. (C) CTLA-4 expression in healthy controls and responders with I-II and III-IV acute GVHD before and after treatment measured by ELISA. (D) CTLA-4 expression in healthy controls and responders with I-II and III-IV acute GVHD before and after treatment measured by q-PCR. Biology of Blood and Marrow Transplantation 2016 22, 212-219DOI: (10.1016/j.bbmt.2015.11.003) Copyright © 2016 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Changes in STAT3 luciferase activity after up-regulation of CTLA-4. Biology of Blood and Marrow Transplantation 2016 22, 212-219DOI: (10.1016/j.bbmt.2015.11.003) Copyright © 2016 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Changes in STAT3 and pSTAT3 protein expression after up-regulation of CTLA-4. Biology of Blood and Marrow Transplantation 2016 22, 212-219DOI: (10.1016/j.bbmt.2015.11.003) Copyright © 2016 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Changes in the degree of STAT3 phophorylation after up-regulation of CTLA-4. Biology of Blood and Marrow Transplantation 2016 22, 212-219DOI: (10.1016/j.bbmt.2015.11.003) Copyright © 2016 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 6 Changes in proliferation of CD4+ T cells after up-regulation of CTLA-4. *P < .01, compared with the blank control group. #P < .05, compared with the FLAG group. Biology of Blood and Marrow Transplantation 2016 22, 212-219DOI: (10.1016/j.bbmt.2015.11.003) Copyright © 2016 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 7 Changes in apoptosis of CD4+ T cells after up-regulation of CTLA-4. Biology of Blood and Marrow Transplantation 2016 22, 212-219DOI: (10.1016/j.bbmt.2015.11.003) Copyright © 2016 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 8 Changes in secretion of IFN-γ (A), IL-4 (B), IL-17 (C), and IL-22 (D) after up-regulation of CTLA-4. Biology of Blood and Marrow Transplantation 2016 22, 212-219DOI: (10.1016/j.bbmt.2015.11.003) Copyright © 2016 American Society for Blood and Marrow Transplantation Terms and Conditions