Regulation of CD40 ligand expression in systemic lupus erythematosus

Production of pathogenic autoantibodies in systemic lupus erythematosus (SL E) requires T cell help, along with ligation of the B cell surface immunogl obulin receptor by antigen. It is likely that macrophages, dendritic cells, and endothelial cells are also activated by interactions with T cells and contribute to lupus pathology. CD40 ligand (CD40L, CD154), a member-of the tumor necrosis factor family of cell surface molecules, mediates these cont act dependent signals delivered by CD4(+) T helper cells to CD40(+) target cells. Recent data from SLE patients and murine lupus models have demonstra ted prolonged expression of CD40L on lupus T cells and its capacity to medi ate excessive B cell activation. This review summarizes the current informa tion regarding transcriptional and post-transcriptional regulation of CD40L expression in normal and SLE T cells. More complete characterization of th e mechanisms that regulate the magnitude and duration of CD40L expression s hould suggest new approaches to modulate this promising therapeutic target. (C) 2001 Lippincott Williams & Wilkins, Inc.