Bronchial asthma is an emerged chronic inflammatory disorder of the airway characterized by airway hyperresponsiveness (AHR), pulmonary eosinophilia, elevated serum immunoglobulin (Ig) E, and dysregulated T helper (Th) 2 cytokines. It is becoming urgent to identify target molecules for the preventive and therapeutic purpose. Non-depleting YTS177 anti-CD4 monoclonal antibody (MoAb) has been used to induce immunotolerance in allograft transplantation through antigen-specific Treg cells. This study aims for determining whether YTS177 MoAb is able to inhibit the ovalbumin (OVA)-induced allergic inflammation in an asthmatic murine model. The injection of YTS177 MoAb before and after OVA-sensitization was able to suppress AHR, pulmonary eosinophilia, OVA-specific IgE synthesis, and the production of Th2 cytokines from OVA-activated splenocytes. YTS177 MoAb inhibited the proliferation of DO11.10 CD4+ T cells upon in vivo OVA-stimulation as well. Moreover, YTS177 MoAb-treatment sustained the protein levels of anergy factors, p27kip1 and Cbl-b, and inhibited IL-2 production and cell cycle progression in activated T cells in vitro. The tolerance status might be built on YTS177 MoAb-induced CD4 down regulation and raft dissociation through clathrin-dependent manner. Collectively, YTS177 MoAb binding causes CD4 internalization that further perturbs T cell receptor signaling and ultimately results T cell unresponsiveness.
- Copyright © 2013 by The American Association of Immunologists, Inc.