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

Cheng-Jang Wu; Chun-Hao Lu; Li-Chen Chen; Duc T Nguyen; Yi-Shu Huang; Hsi-Hsien Lin; Chun-Yen Lin; Ming-Ling Kuo

doi:10.1016/j.bbrc.2016.04.001

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

Biochem Biophys Res Commun. 2016 May 13;473(4):973-979. doi: 10.1016/j.bbrc.2016.04.001. Epub 2016 Apr 1.

Authors

Cheng-Jang Wu¹, Chun-Hao Lu², Li-Chen Chen³, Duc T Nguyen⁴, Yi-Shu Huang², Hsi-Hsien Lin⁵, Chun-Yen Lin⁶, Ming-Ling Kuo⁷

Affiliations

¹ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093, USA.
² Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
³ Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
⁴ Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093, USA.
⁵ Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; 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.
⁶ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; 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.
⁷ Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; 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. Electronic address: [email protected].

PMID: 27045081
DOI: 10.1016/j.bbrc.2016.04.001

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(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(+) 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.

Keywords: Anergy; Asthma; Lipid raft; T cell unresponsiveness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / pharmacology*
CD4 Antigens / immunology*
CD4 Antigens / metabolism
Cell Proliferation / drug effects
Clonal Anergy*
Down-Regulation
Female
Membrane Microdomains / metabolism
Mice, Inbred BALB C
T-Lymphocytes, Helper-Inducer / drug effects
T-Lymphocytes, Helper-Inducer / immunology*

Substances

Antibodies, Monoclonal
CD4 Antigens