Immature dendritic cells expressing indoleamine 2,3-dioxygenase suppress ovalbumin-induced allergic airway infl ammation in mice

Background: proliferation of activated cd4+ t lymphocytes is inhibited by indoleamine 2,3-dioxygenase (ido). objective: we undertook the present study to test the hypothesis that ido-expressing immature dcs (imdcs) can restore immune tolerance in mice suffering from allergic airway infl ammation. methods: imdcs were generated from murine bone marrow cells using granulocyte-macrophage colony-stimulating factor. the imdcs were subsequently transfected with an ido expression vector (pegfp-n1-ido). surface marker expression,including cd11c,mhc ii,cd80,and cd86,was analyzed using fl ow cytometry. ido-expressing imdcs were injected into the trachea of ovalbumin (ova)-sensitized mice,and lung histopathology and cytokine expression in bronchoalveolar lavage fl uid were assessed. the splenic cd4+ t cells of ova-sensitized mice were isolated and co-cultured with pegfp-n1-ido-expressing imdcs,and apoptosis of cd4+ t cells was detected using the terminal deoxynucleotidyl transferase dutp nick end labeling assay. results: expression of ido in imdcs did not alter cell surface molecule expression. we observed marked lung infl ammation,elevated total cell and eosinophil count,and altered cytokine levels in ova-sensitized mice. these parameters improved upon inoculation with idoexpressing imdcs. co-culture with ido-expressing imdcs also induced apoptosis,inhibited il-4 and il-5 expression,and upregulated ifn-γ expression in cd4+ t cells. conclusions: ido-expressing imdcs induced th2 cell apoptosis and reduced th2 cell activation and allergic airway infl ammation in ovasensitized mice. thus,upregulation of ido expression may provide a novel immunointervention strategy for asthma treatment. © 2011 esmon publicidad.