The mechanisms of non-depleting YTS177 anti-CD4 monoclonal antibody in controlling ovalbumin-induced asthmatic responses (P6017)

Abstract

Abstract 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.