Dynamic monitoring of pathological and immunological changes and treatment effect of killer artificial antigen presenting cells in a murine experimental autoimmune encephalomyelitis model

Abstract

Abstract Multiple sclerosis (MS) is a chronic, autoimmune disease of the central nervous system. Experimental autoimmune encephalomyelitis (EAE) are widely used to study the pathological features and mechanisms underlying MS. Here, a murine EAE model was induced. The disease degree was daily assessed; The local inflammatory infiltration was observed and the expressions of MBP and GFAP were detected. The frequencies and reactivity of MOG antigen-specific CD4+ T cell and CD8+ T cells were concurrently investigated. As a result, the dynamic changes of inflammation, myelin loss and astrocyte proliferation in CNS were highly consistent with clinical manifestations observed in EAE course. Data also emphasize the pathogenic roles of both CD4+ T cells and CD8+T cells in the development of EAE, while their reactivity in response to the antigen was different from their dynamic changes of frequencies. Killer artificial antigen presenting cells (KaAPCs) are thought to be a powerful tool to inhibit autoimmune effect and kill autoreactive T cells avoiding systemic immune suppression. Here, a KaAPC was generated by covalently co-coupling targeted binding molecules (H-2Db/MOG40-54 dimmer, H-2I-Ab/MOG35-55 multimer), negative regulation molecules (anti-mouse Fas mAbs, PD-L1-Ig, TGF-β1) and antiphagecytic molecules (CD47-Ig) onto poly lactic-co-glycolic acid (PLGA) microspheres. We found decreased clinical score of EAE mice after several times treatment of KaAPCs. Collectively, this study presented a clear histopathologic and immunologic pattern of mouse EAE model, which may contribute to better understanding of the EAE process. Also, KaAPCs are feasible strategy for treating EAE, which lead to a new approach for MS therapies.