Inhibition of allogeneic T-cell responses by dendritic cells expressing transduced indoleamine 2,3-dioxygenase.

Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in the catabolism of tryptophan and has been shown to prevent rejection of the fetus during pregnancy by inhibiting alloreactive T cells. In this study we investigated dendritic cells (DCs) that are transfected with IDO cDNA in the inhibition of T-cell proliferation after antigen-specific interaction. XS106 DCs, derived from A/J mice (H-2k), were transduced with IDO with a gene-delivery system using a recombinant adenoviral vector. Western blotting and immune staining revealed IDO expression in XS106 DCs transduced with IDO (XS106-IDO DCs), and its catabolic effect was confirmed by an increase in kynurenine concentration. Fluorescence-activated cell sorting revealed that XS106-IDO DCs were not changeable for Ia, CD80, and CD86 expression. After XS106-IDO DCs were co-cultured with C57BL/6 allogeneic splenic T cells, the proliferation of the T cell was significantly inhibited. The co-cultured T cells with XS106-IDO DCs exhibited cell-cycle arrest. Furthermore, injection of XS160-IDO DCs into the footpads of C57BL/6 (H-2b) mice demonstrated a reduced T-cell response against allo-antigen. These results suggest that overexpression of IDO in the DCs effectively inhibited T-cell proliferation, and may expand a new immunomodulatory strategy for the prevention of allo-rejection of organ transplantation.

Funeshima N ，Fujino M ，Kitazawa Y ，Hara Y ，Hara Y ，Hayakawa K ，Okuyama T ，Kimura H ，Li XK ... -  《JOURNAL OF GENE MEDICINE》

A minor population of splenic dendritic cells expressing CD19 mediates IDO-dependent T cell suppression via type I IFN signaling following B7 ligation.

Baban B ，Hansen AM ，Chandler PR ，Manlapat A ，Bingaman A ，Kahler DJ ，Munn DH ，Mellor AL ... -  《INTERNATIONAL IMMUNOLOGY》

GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase.

Munn DH ，Sharma MD ，Baban B ，Harding HP ，Zhang Y ，Ron D ，Mellor AL ... -  《IMMUNITY》

Are indoleamine-2,3-dioxygenase producing human dendritic cells a tool for suppression of allogeneic T-cell responses?

Löb S ，Ebner S ，Wagner S ，Weinreich J ，Schäfer R ，Königsrainer A ... -  《TRANSPLANTATION》

Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase.

Mellor AL ，Chandler P ，Baban B ，Hansen AM ，Marshall B ，Pihkala J ，Waldmann H ，Cobbold S ，Adams E ，Munn DH ... -  《INTERNATIONAL IMMUNOLOGY》