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(Journal of Leukocyte Biology. 2001;70:723-729.)
© 2001 by Society for Leukocyte Biology

Muramyl dipeptide-Lys stimulates the function of human dendritic cells

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

Correspondence: Kingo Chida, M.D., Ph.D., 3600 Handa-cho, Hamamatsu, Shizuoka 431-3192 Japan. E-mail: chidak11{at}hama-med.ac.jp

Muramyl dipeptide (MDP)-Lys (L18), a synthetic MDP analogue derived from bacterial cell walls, has been reported to be a potent immunoadjuvant that enhances protective immunity against pathogens and tumors by stimulating immune-competent cells, such as monocytes and macrophages. However, it is not known whether MDP-Lys modulates the function of dendritic cells (DCs), which are the most potent antigen-presenting cells and play a crucial role in initiating T cell-mediated immunity. Therefore, we examined the effects of MDP-Lys on the expression of surface molecules, cytokine production, and antigen-presenting function of human DCs generated from peripheral blood cells in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. We found that MDP-Lys markedly up-regulated the expression of CD80, CD83, CD86, and CD40, but not human leukocyte antigen-DR, and stimulated the production of tumor necrosis factor-, IL-6, IL-8, IL-10, and IL-12 (p40) by human DCs in a dose-dependent manner. Furthermore, MDP-Lys-treated DCs showed enhanced antigen-presenting function compared with untreated DCs, as assessed by an allogeneic mixed lymphocyte reaction. These results suggested that the immunoadjuvant activity of MDP-Lys in vivo is mediated, in part, by its stimulation of DC function.

Key Words: immunoadjuvant activity • antigen-presenting cells • T cell immunity

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