PMID- 12350510 OWN - NLM STAT- MEDLINE DCOM- 20021115 LR - 20190714 IS - 1527-9995 (Electronic) IS - 0090-4295 (Linking) VI - 60 IP - 3 DP - 2002 Sep TI - An Escherichia coli-based oral vaccine against urinary tract infections potently activates human dendritic cells. PG - 521-6 AB - OBJECTIVES: To investigate the effects of Uro-Vaxom, an oral vaccine against Escherichia coli urinary tract infections, on human monocyte-derived dendritic cells (moDCs). Dendritic cells (DCs) are important antigen-presenting cells of the immune system. DCs are considered promising cellular adjuvants for inducing immunity against cancer or infectious diseases. METHODS: moDCs were generated in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. Flow cytometric phenotyping, as well as the ability to stimulate T cells in an allogeneic mixed leukocyte reaction, was used to assess the effects of Uro-Vaxom on human moDCs. In addition, interferon-gamma and interleukin-4 production by T cells stimulated with Uro-Vaxom-activated moDCs were measured by intracellular fluorescence-activated cell sorter-staining at the single-cell level. RESULTS: Uro-Vaxom induced the terminal maturation of CD83+ moDCs in a dose-dependent manner. Phenotypic analyses revealed that Uro-Vaxom-activated moDCs displayed a phenotype of mature DCs with high levels of MHC molecules and increased levels of co-stimulatory molecules (CD80, CD86). Consistent with these findings, Uro-Vaxom-activated moDCs potently stimulated T-cell proliferation and interferon-gamma production in the allogeneic mixed leukocyte reaction. CONCLUSIONS: In DC-based immunotherapy, Uro-Vaxom could be used as a stimulant of DC maturation, which meets the standards of good manufacturing practice. In future preclinical studies, we will evaluate the effectiveness of a vaccination with Uro-Vaxom-activated moDCs. It could be an attractive treatment option in preventing recurrent E. coli urinary tract infections in predisposed individuals. FAU - Schmidhammer, Silvia AU - Schmidhammer S AD - Department of Urology, University of Innsbruck, Innsbruck, Austria. FAU - Ramoner, Reinhold AU - Ramoner R FAU - Holtl, Lorenz AU - Holtl L FAU - Bartsch, Georg AU - Bartsch G FAU - Thurnher, Martin AU - Thurnher M FAU - Zelle-Rieser, Claudia AU - Zelle-Rieser C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Urology JT - Urology JID - 0366151 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antigens, CD) RN - 0 (Escherichia coli Vaccines) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adjuvants, Immunologic/*pharmacology/therapeutic use MH - Antigens, CD/immunology MH - Cells, Cultured MH - Dendritic Cells/drug effects/*immunology MH - Dose-Response Relationship, Immunologic MH - Escherichia coli/immunology MH - Escherichia coli Infections/immunology/prevention & control MH - Escherichia coli Vaccines/*pharmacology/therapeutic use MH - Flow Cytometry MH - Humans MH - Immunophenotyping MH - Interferon-gamma/immunology MH - Lymphocyte Culture Test, Mixed MH - Monocytes/immunology MH - Urinary Tract Infections/immunology/prevention & control EDAT- 2002/09/28 04:00 MHDA- 2002/11/26 04:00 CRDT- 2002/09/28 04:00 PHST- 2002/09/28 04:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/09/28 04:00 [entrez] AID - S0090429502017673 [pii] AID - 10.1016/s0090-4295(02)01767-3 [doi] PST - ppublish SO - Urology. 2002 Sep;60(3):521-6. doi: 10.1016/s0090-4295(02)01767-3.