1. Induction of IL-10 producing CD4+ T cells with regulatory activities by stimulation with IL-10 gene-modified bone marrow derived dendritic cells
- Author
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Bor-Luen Chiang, Ya-Hui Chuang, Hsin Yi Huang, and Fu Cl
- Subjects
CD4-Positive T-Lymphocytes ,Genetic Vectors ,Immunology ,Bone Marrow Cells ,Mice, Transgenic ,Biology ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,Adenoviridae ,Immune tolerance ,Interferon-gamma ,Mice ,Interleukin 21 ,Basic Immunology ,Transduction, Genetic ,Immune Tolerance ,Animals ,Immunology and Allergy ,Cytotoxic T cell ,IL-2 receptor ,Interleukin 3 ,Mice, Inbred BALB C ,Follicular dendritic cells ,Cell Differentiation ,Dendritic Cells ,Dendritic cell ,Coculture Techniques ,Interleukin-10 ,Interleukin 12 ,Female - Abstract
Summary 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 naïve 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-γ upon restimulation with irradiated splenocytes and ovalbumin peptide. Furthermore, in co-culture experiments these T cells inhibited the antigen-driven proliferation of naïve 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.
- Published
- 2008