THE APPLICATION OF THE DENDRITIC CELL GENE THERAPY IN TRANSPLANTATION FIELD -Induction of antigen-specific T cell proliferation by Indoleamine 2,3-dioxygenase cDNA-transfected dendritic cells-

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Purpose : Indoleamine 2,3-dioxygenase (IDO) is an enzyme, involved in the catabolism of tryptophan and has been show to prevent rejection of the fetus during pregnancy, probably by inhibiting alloreactive T cells. In the present study, we investigated whether DCs that are transfected with IDO cDNA in inhibition of T cell proliferation after antigen-specific interaction. Methods : IDO was expressed with a gene delivery system using a recombinantadenoviral vector and its expression and function were confirmed by Western blot, immunology staining and kynurenine assay. The expression of the surface molecular of the IDO-transfected XS106 DC clone (derived from A/J mice) was confirmed by FACS analysis. Alloreactive T cell proliferation was assayed after culture with IDO-expressed DC. Results : A recombinant adenoviral vector expressing IDO was successfully generated and its gene expression detected by Western blot and immune staining. Its catabolic effect was confirmed by increase the kynurenine concentration. It revealed that IDO-expressing XS106 DC were no changeable for CD86, CDllc and CD69 expression. After co-cultured IDO-expressing DC with B6 allogeneic splenic T cell, the proliferation of the T cell was inhibited significantly. Conclusions : These results suggest that over expression of the IDO in the DC was effective to inhibit T cell proliferation, and may expand a new immunomodulatory strategy to prevent the allo-rejection of the organ transplantation.