T cells in the pathogenesis of systemic lupus erythematosus: potential roles of CD154-CD40 interactions and costimulatory molecules.

CD154 is an activation-induced CD4+ T cell surface molecule that interacts with CD40 on antigen-presenting cells (APC) and upregulates the key costimulatory molecules, CD80 and CD86. Bidirectional intercellular signaling mediated by CD40 ligation and CD80/CD86 interactions with counter-receptors on T cells play central roles in regulating the survival and outgrowth of pathogenic autoreactive T cells and B cells in systemic lupus erythematosus (SLE). CD40 is also expressed on a variety of other cells, including endothelial cells and renal tubule epithelial cells. CD154 activation of APCs, endothelial cells, and renal tubular epithelial cells have proinflammatory or procoagulant effects that may contribute to the pathogenesis of lupus. This review will focus on the immunobiology of CD154-CD40 interactions and the costimulatory functions of CD80 and CD86. The experimental evidence suggesting roles for these molecules in the immunopathogenesis of SLE will be reviewed.