PMID- 18549444 OWN - NLM STAT- MEDLINE DCOM- 20080915 LR - 20211020 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 153 IP - 2 DP - 2008 Aug TI - Induction of IL-10 producing CD4+ T cells with regulatory activities by stimulation with IL-10 gene-modified bone marrow derived dendritic cells. PG - 258-68 LID - 10.1111/j.1365-2249.2008.03689.x [doi] AB - Dendritic cells (DCs) can induce both tolergenic as well as effective immune responses in the lung. Pulmonary DCs producing interleukin (IL)-10 mediated tolerance induced by respiratory exposure to antigen. IL-10 is an important immunosuppressive cytokine, which inhibits maturation and function of DC. To assess whether IL-10 producing DCs can exert the tolergenic effect through the differentiation of regulatory T cells, bone marrow derived DCs were genetically modified by IL-10 expressing adenovirus. IL-10 gene modified DCs (Ad-IL-10-DC) displayed a characteristic phenotype of immature DCs. Here we showed that in vitro repetitive stimulation of naive DO11.10 CD4(+) T cells with Ad-IL-10-DCs resulted in a development of IL-10 producing T-cell regulatory cells. These T cells could not proliferate well but also lost their ability to produce interferon-gamma upon restimulation with irradiated splenocytes and ovalbumin peptide. Furthermore, in co-culture experiments these T cells inhibited the antigen-driven proliferation of naive CD4+ T cells in a dose-dependent manner. Our findings demonstrated that IL-10 producing DCs had the potential to induce the differentiation of Tr1-like cells and suggested their therapeutic use. FAU - Fu, C-L AU - Fu CL AD - Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taiwan, ROC. FAU - Chuang, Y-H AU - Chuang YH FAU - Huang, H-Y AU - Huang HY FAU - Chiang, B-L AU - Chiang BL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080628 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adenoviridae/genetics MH - Animals MH - Bone Marrow Cells/immunology MH - CD4-Positive T-Lymphocytes/*immunology MH - Cell Differentiation MH - Coculture Techniques MH - Dendritic Cells/*immunology MH - Female MH - Genetic Vectors/genetics/pharmacology MH - Immune Tolerance MH - Interferon-gamma/immunology MH - Interleukin-10/genetics/*immunology MH - Lymphocyte Activation MH - Mice MH - Mice, Inbred BALB C MH - Mice, Transgenic MH - T-Lymphocytes, Regulatory/*immunology MH - Transduction, Genetic/methods PMC - PMC2492900 EDAT- 2008/06/14 09:00 MHDA- 2008/09/16 09:00 PMCR- 2009/08/01 CRDT- 2008/06/14 09:00 PHST- 2008/06/14 09:00 [pubmed] PHST- 2008/09/16 09:00 [medline] PHST- 2008/06/14 09:00 [entrez] PHST- 2009/08/01 00:00 [pmc-release] AID - CEI3689 [pii] AID - 10.1111/j.1365-2249.2008.03689.x [doi] PST - ppublish SO - Clin Exp Immunol. 2008 Aug;153(2):258-68. doi: 10.1111/j.1365-2249.2008.03689.x. Epub 2008 Jun 28.