CD40LG expression is mainly confined to the CD4-positive-T-cell subset. Its expression is induced shortly after T-cell activation and represents an early activation marker of T lymphocytes. CD40 is constitutively expressed mainly on B cells, macrophages, and dendritic cells. The CD40-CD40L pathway has been shown to play multiple functional roles in the healthy immune system. It enhances the antigen-specific T-cell response through the activation of dendritic cells and the induction of interleukin-12 production. For example, engagement of CD40 on endothelial cells by activated T cells expressing CD40L leads to upregulation of adhesion molecules such as ICAM-1, VCAM-1, and E-selectin. Activation of APC by CD40-CD40L interaction induces the production of inflammatory cytokines, chemokines, NO, and metalloproteinases. Interaction of CD4-positiveCD40LG-positiveT cells with CD40 on B cells leads to B-cell differentiation, proliferation, immunoglobulin (Ig) isotype switching, and formation of memory B cells.