CD40 EXPRESSION BY HUMAN MONOCYTES - REGULATION BY CYTOKINES AND ACTIVATION OF MONOCYTES BY THE LIGAND FOR CD40

CD40 is a member of the tumor necrosis factor (TNF) receptor family of cell surface proteins and was originally described as a B cell restri cted antigen. Treatment of primary human monocytes with granulocyte/ma crophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), or interferon gamma (IFN-gamma) resulted in the induction of CD40 mRNA an d enhancement of cell surface protein expression. CD40 was found to me diate monocyte adhesion to cells expressing recombinant CD40 ligand. C D40 ligand-transfected cells provided a potent costimulus for monocyte TNF-alpha and IL-6 production in the presence of GM-CSF, IL-3, or IFN -gamma, and enhanced IL-8 production stimulated by GM-CSF or IL-3. In addition, CD40 ligand-transfected cells acting in the absence of a cos timulus induced monocytes to become tumoricidal against a human melano ma cell target. Collectively, these data indicate that CD40 ligand is pleiotropic with potent biological activity on monocytes.