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(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.
authors.affiliation: 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.
authors.forename: Cheng-Jang
authors.initials: CJ
authors.lastname: Wu
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Lu
authors.affiliation: Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Chen
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093, USA.
authors.forename: Duc T
authors.initials: DT
authors.lastname: Nguyen
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yi-Shu
authors.initials: YS
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Lin
authors.affiliation: 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: mingling@mail.cgu.edu.tw.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Kuo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D017635:Clonal Anergy; D015536:Down-Regulation; D005260:Female; D021962:Membrane Microdomains / Q000378:metabolism; D008807:Mice, Inbred BALB C; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens
keywords: Anergy; Asthma; Lipid raft; T cell unresponsiveness