Induction of Il-10 Producing Cd4+ T Cells with Regulatory Activities by Stimulation with Il-10 Gene-Modified Bone Marrow Derived Dendritic Cells
Resource
CLINICAL AND EXPERIMENTAL IMMUNOLOGY v.153 n.2 pp.258-268
Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Journal Volume
v.153
Journal Issue
n.2
Pages
258-268
Date Issued
2008
Date
2008
Author(s)
FU, CHI-LING
CHUANG, YA-HUI
HUANG, HSIN -YING
CHIANG, BOR-LUEN
Abstract
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-gamma 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.
Subjects
dendritic cells
IL-10
regulatory T cells