ABSTRACT
CD40 is a cell surface receptor that belongs to the tumor necrosis factor (TNF) receptor superfamily and was initially shown to be critical for mediating contact-dependent signals between В and T cells. Thus, early studies have established that interactions of CD40 with its ligand, CD 154 (CD40L), a TNF superfamily member are essential for generation of thymus de pendent (TD) humoral immune responses. Recent studies demonstrate that CD40 is not only expressed on В cells but also on dendritic cells, follicular dendritic cells, monocytes, macrophages, mast cells, fibroblasts and endothelial cells. Likewise, expression of CD 154 has also recently been demonstrated on many cells types beyond T cells as originally thought. Studies with CD40-and CD 154-knockout mice and blocking antibodies to interfere with CD40-CD154 interaction have elucidated the role of CD 40-CD154 in many aspects of the immune system. These studies have established a key role of CD40-CD154 in regulation of immunity and autoimmunity and have firmly established the basis for many preclinical and clinical investigations. This article focuses on major and newly discovered find ings for a role of CD40-CD154 in the regulation of many functions in the im mune system and applications of this system for a therapeutic utility.
