Muramyl dipeptide-Lys stimulates the function of human dendritic cells

Muramyl dipeptide (MDP)-Lys (L18), a synthetic MDP analogue derived from ba cterial cell walls, has been reported to be a potent immunoadjuvant that en hances protective immunity against pathogens and tumors by stimulating immu ne-competent cells, such as monocytes and macrophages. However, it is not k nown whether MDP-Lys modulates the function of dendritie cells (DCs), which are the most potent antigen-presenting cells and play a crucial role in in itiating T cell-mediated immunity. Therefore, we examined the effects of MD P-Lys on the expression of surface molecules, cytokine production, and anti gen-presenting function of human DCs generated from peripheral blood cells in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-sti mulating factor. We found that MDP-Lys markedly up-regulated the expression of CD80, CD83, CD86, and CD40, but not human leukocyte antigen-DR, and sti mulated the production of tumor necrosis factor-alpha, IL-6, IL-8, IL-10, a nd IL-12 (p40) by human DCs in a dose-dependent manner. Furthermore, MDP-Ly s-treated DCs showed enhanced antigen-presenting function compared with unt reated DCs, as assessed by an allogeneic mixed lymphocyte reaction. These r esults suggested that the immunoadjuvant activity of MDP-Lys in vivo is med iated, in part, by its stimulation of DC function.