PMID- 17660499 OWN - NLM STAT- MEDLINE DCOM- 20071214 LR - 20220129 IS - 0953-8178 (Print) IS - 0953-8178 (Linking) VI - 19 IP - 9 DP - 2007 Sep TI - IL-10 permits transient activation of dendritic cells to tolerize T cells and protect from central nervous system autoimmune disease. PG - 1123-34 AB - Dendritic cells (DCs) are key players in the development of immunity. They can direct both the size and the quality of an immune response and thus are attractive tools to mediate immunotherapy. DC function has been thought to reflect the cells' maturation, with immunosuppressive agents such as IL-10 understood to retain DCs in an immature and tolerogenic state. Here we report that DC activated in the presence of IL-10 do show functional and phenotypic maturation. Their activation is transient and occurs earlier and more briefly than in cells matured with LPS alone. Despite initially equivalent up-regulation of surface MHC and co-stimulation, the IL-10-treated DCs expressed little IL-12 and failed to stimulate T cell proliferation both in vitro and in vivo. Interaction with IL-10-treated DCs rendered antigen-specific T cells unresponsive to subsequent challenge and their injection reduced the severity of experimental autoimmune disease. Our data suggest that IL-10 acts not by inhibiting maturation but instead by controlling the kinetics and the quality of DC activation. This alternative pathway of DC differentiation offers significant therapeutic promise. FAU - Perona-Wright, Georgia AU - Perona-Wright G AD - Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, UK. FAU - Anderton, Stephen M AU - Anderton SM FAU - Howie, Sarah E M AU - Howie SE FAU - Gray, David AU - Gray D LA - eng GR - G117/515/MRC_/Medical Research Council/United Kingdom GR - 068937/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070728 PL - England TA - Int Immunol JT - International immunology JID - 8916182 RN - 0 (Lipopolysaccharides) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - Cell Differentiation/drug effects/immunology MH - Cells, Cultured MH - Dendritic Cells/*drug effects/immunology MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Immune Tolerance/*drug effects MH - Immunophenotyping MH - Interleukin-10/physiology/*therapeutic use MH - Interleukin-12/biosynthesis MH - Lipopolysaccharides/pharmacology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Multiple Sclerosis/*drug therapy/immunology MH - T-Lymphocytes/*drug effects/immunology MH - Time Factors EDAT- 2007/07/31 09:00 MHDA- 2007/12/15 09:00 CRDT- 2007/07/31 09:00 PHST- 2007/07/31 09:00 [pubmed] PHST- 2007/12/15 09:00 [medline] PHST- 2007/07/31 09:00 [entrez] AID - dxm084 [pii] AID - 10.1093/intimm/dxm084 [doi] PST - ppublish SO - Int Immunol. 2007 Sep;19(9):1123-34. doi: 10.1093/intimm/dxm084. Epub 2007 Jul 28.