title: Inhibition of allogeneic T-cell responses by dendritic cells expressing transduced indoleamine 2,3-dioxygenase.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Transplantation Immunology, Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Funeshima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujino
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kitazawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hara
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hara
authors.forename: Kou
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Torayuki
authors.initials: T
authors.lastname: Okuyama
authors.forename: Hiromitus
authors.initials: H
authors.lastname: Kimura
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D018920:Coculture Techniques; D018076:DNA, Complementary / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology; D005260:Female; D015316:Genetic Therapy; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic; D014366:Tryptophan Oxygenase / Q000235:genetics* / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014366:Tryptophan Oxygenase