PMID- 18408138 OWN - NLM STAT- MEDLINE DCOM- 20080708 LR - 20231213 IS - 1535-3702 (Print) IS - 1535-3699 (Linking) VI - 233 IP - 6 DP - 2008 Jun TI - 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-beta. PG - 721-31 LID - 10.3181/0712-RM-333 [doi] AB - 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)-beta 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)-alpha, but not IL-10. 4B-DCs promoted proliferation of allogeneic naive CD4(+) T cells, producing IFN-(lambda) at lower levels than those stimulated with G4-DCs. 4B-DCs were more potent stimulators of allogeneic bulk CD8(+) T cells producing IFN-(lambda) 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. FAU - Zhang, Li Feng AU - Zhang LF AD - Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Uehara 207, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan. FAU - Okuma, Kazu AU - Okuma K FAU - Tanaka, Reiko AU - Tanaka R FAU - Kodama, Akira AU - Kodama A FAU - Kondo, Kayo AU - Kondo K FAU - Ansari, Aftab A AU - Ansari AA FAU - Tanaka, Yuetsu AU - Tanaka Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080411 PL - Switzerland TA - Exp Biol Med (Maywood) JT - Experimental biology and medicine (Maywood, N.J.) JID - 100973463 RN - 0 (Antigens, CD) RN - 0 (B7-1 Antigen) RN - 0 (B7-2 Antigen) RN - 0 (CD11c Antigen) RN - 0 (Immunoglobulins) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 207137-56-2 (Interleukin-4) RN - 77238-31-4 (Interferon-beta) SB - IM MH - Antigens, CD/biosynthesis MH - B7-1 Antigen/biosynthesis MH - B7-2 Antigen/biosynthesis MH - CD11c Antigen/biosynthesis MH - Cell Culture Techniques/methods MH - Cells, Cultured MH - Dendritic Cells/*metabolism MH - *Gene Expression Regulation MH - Humans MH - Immune System MH - Immunoglobulins/biosynthesis MH - Interferon-beta/*metabolism MH - Interleukin-4/*metabolism MH - Lipopolysaccharides/metabolism MH - Membrane Glycoproteins/biosynthesis MH - Monocytes/*metabolism MH - Phenotype MH - CD83 Antigen EDAT- 2008/04/15 09:00 MHDA- 2008/07/09 09:00 CRDT- 2008/04/15 09:00 PHST- 2008/04/15 09:00 [pubmed] PHST- 2008/07/09 09:00 [medline] PHST- 2008/04/15 09:00 [entrez] AID - 0712-RM-333 [pii] AID - 10.3181/0712-RM-333 [doi] PST - ppublish SO - Exp Biol Med (Maywood). 2008 Jun;233(6):721-31. doi: 10.3181/0712-RM-333. Epub 2008 Apr 11.