CD40 expression on specific antigen-presenting cells mediates experimental autoimmune encephalomyelitis

Abstract

Abstract CD40 is a cell surface receptor that belongs tothe tumor necrosis factor receptor (TNFR) family and serves as a costimulatory molecule on the antigen presenting cells (APCs). The interaction between CD40 on B cells and its ligand CD154 on activated T helper cells is known to be essential for the development of thymus-dependent humoral immunity. Administration of blocking anti-CD40L antibody or CD40 gene knockout make mice resistant to experimental autoimmune encephalomyelitis(EAE), an animal model of human multiple sclerosis (MS), but the complex cellular interactions mediating the role of CD40 in EAE are not fully understood. We are using conditional CD40 knockout mice to selectively delete CD40 on specific APC populations and evaluate the effects by recombinant human MOG (rhMOG) induced EAE, a model is both T cell and B cell dependent. We found that conditional knockout of CD40 on B cells or dendritic cells led to significantly reduced severity of EAE. Studies of the mechanisms mediating CD40 function in immune response and CNS immunopathology are underway.