skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: CD4 down regulation and raft dissociation by the non-depleting YTS177 antibody hinder murine T helper cell activities

Abstract

Non-depleting YTS177 anti-CD4 monoclonal antibody (MoAb) has been reported to lead to antigen-specific immunotolerance in allograft transplantation and autoimmune diabetes, as well as possibly to inhibition of allergic inflammation in mice. However, the molecular mechanisms underlying hyporesponsive T cell responses induced by YTS177 MoAb remain elusive. Herein, we demonstrate that the YTS177 MoAb increases the levels of anergy factors p27{sup kip1} and Cbl-b, inhibits IL-2 production, and impairs calcium mobilization in activated T cells in vitro. YTS177 MoAb suppresses OVA-driven proliferation of DO11.10 CD4{sup +} T cells in vivo as well. Mechanistically, YTS177 MoAb induces tolerance by causing CD4 down-regulation through clathrin-dependent and raft dissociation. The results obtained in this study lead us to propose novel protective or curative approaches to CD4 T cell-mediated diseases.

Authors:
 [1];  [1];  [2];  [3];  [1];  [4];  [1];  [4]
  1. Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan (China)
  2. Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan (China)
  3. Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093 (United States)
  4. Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan (China)
Publication Date:
OSTI Identifier:
22596384
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 473; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIGENS; ASTHMA; CALCIUM; CELL PROLIFERATION; GENE REGULATION; IN VITRO; IN VIVO; INFLAMMATION; INHIBITION; LIPIDS; MICE; MONOCLONAL ANTIBODIES; OVA

Citation Formats

Wu, Cheng-Jang, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093, Lu, Chun-Hao, Chen, Li-Chen, Nguyen, Duc T., Huang, Yi-Shu, Lin, Hsi-Hsien, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan, Department of Anatomic Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Lin, Chun-Yen, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Kuo, Ming-Ling, Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, and Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan. CD4 down regulation and raft dissociation by the non-depleting YTS177 antibody hinder murine T helper cell activities. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.04.001.
Wu, Cheng-Jang, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093, Lu, Chun-Hao, Chen, Li-Chen, Nguyen, Duc T., Huang, Yi-Shu, Lin, Hsi-Hsien, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan, Department of Anatomic Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Lin, Chun-Yen, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Kuo, Ming-Ling, Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, & Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan. CD4 down regulation and raft dissociation by the non-depleting YTS177 antibody hinder murine T helper cell activities. United States. doi:10.1016/J.BBRC.2016.04.001.
Wu, Cheng-Jang, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093, Lu, Chun-Hao, Chen, Li-Chen, Nguyen, Duc T., Huang, Yi-Shu, Lin, Hsi-Hsien, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan, Department of Anatomic Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Lin, Chun-Yen, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Kuo, Ming-Ling, Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, and Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan. Fri . "CD4 down regulation and raft dissociation by the non-depleting YTS177 antibody hinder murine T helper cell activities". United States. doi:10.1016/J.BBRC.2016.04.001.
@article{osti_22596384,
title = {CD4 down regulation and raft dissociation by the non-depleting YTS177 antibody hinder murine T helper cell activities},
author = {Wu, Cheng-Jang and Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093 and Lu, Chun-Hao and Chen, Li-Chen and Nguyen, Duc T. and Huang, Yi-Shu and Lin, Hsi-Hsien and Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan and Department of Anatomic Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan and Lin, Chun-Yen and Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan and Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan and Kuo, Ming-Ling and Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan and Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan},
abstractNote = {Non-depleting YTS177 anti-CD4 monoclonal antibody (MoAb) has been reported to lead to antigen-specific immunotolerance in allograft transplantation and autoimmune diabetes, as well as possibly to inhibition of allergic inflammation in mice. However, the molecular mechanisms underlying hyporesponsive T cell responses induced by YTS177 MoAb remain elusive. Herein, we demonstrate that the YTS177 MoAb increases the levels of anergy factors p27{sup kip1} and Cbl-b, inhibits IL-2 production, and impairs calcium mobilization in activated T cells in vitro. YTS177 MoAb suppresses OVA-driven proliferation of DO11.10 CD4{sup +} T cells in vivo as well. Mechanistically, YTS177 MoAb induces tolerance by causing CD4 down-regulation through clathrin-dependent and raft dissociation. The results obtained in this study lead us to propose novel protective or curative approaches to CD4 T cell-mediated diseases.},
doi = {10.1016/J.BBRC.2016.04.001},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 473,
place = {United States},
year = {2016},
month = {5}
}