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ORIGINAL RESEARCH ARTICLE

Generation of Mature Dendritic Cells with Unique Phenotype and Function by In Vitro Short-Term Culture of Human Monocytes in the Presence of Interleukin-4 and Interferon-β

Li Feng Zhang^*, Kazu Okuma^*, Reiko Tanaka^*, Akira Kodama^*, Kayo Kondo^*, Aftab A. Ansari and Yuetsu Tanaka^*,1

^* Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Okinawa, Japan; and Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322

To whom requests for reprints should be addressed at ¹ Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Uehara 207, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan. E-mail: yuetsu{at}s4.dion.ne.jp

Dendritic cell (DC)-based immunotherapy has been utilized for the treatment of not only a number of human malignancies but also a select group of infectious diseases. Conventional techniques for the generation and maturation of DCs require 7 days of in vitro culture, which prompted us to seek alternative methods that would hasten the generation of functional human myeloid DCs in vitro. Following the use of a number of cytokines/growth factors, we found that in vitro culture of purified human monocytes, in media containing interleukin (IL)-4, together with interferon (IFN)-β for 24 hrs, followed by the addition of non-specific antigenic stimuli, such as keyhole limpet hemocyanin (KLH), lipopolysaccharide (LPS), or inactivated human immunodeficiency virus (HIV)-1 induced the monocytes to differentiated by 3 days into mature DCs (4B-DCs). These 4B-DCs expressed high levels of CD83 and CD11c, as well as markers of immune activation, including CD80 and CD86, human leukocyte antigen (HLA) class I and II, and CD14, but not CD1a. Anti-CD14 blocking antibody interfered with generation of 4B-DCs by LPS, but not by KLH or HIV-1. Interestingly, 4B-DCs, but not conventional DCs generated using macrophage-colony stimulating factor and IL-4 (G4-DCs), expressed OX40 and OX40L. 4B-DCs showed phagocytic activity, and spontaneously produced IL-12 and tumor necrosis factor (TNF)-, but not IL-10. 4B-DCs promoted proliferation of allogeneic naïve CD4⁺ T cells, producing IFN- at lower levels than those stimulated with G4-DCs. 4B-DCs were more potent stimulators of allogeneic bulk CD8⁺ T cells producing IFN- than G4-DCs. These data indicate that 4B-DCs are unique and may provide a relatively more rapid alternative tool for potential clinical use, as compared with conventional G4-DCs.