Inhibition of allogeneic T-cell responses by dendritic cells expressing transduced indoleamine 2,3-dioxygenase.
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.
Funeshima
Naoko
N
Laboratory of Transplantation Immunology, Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan.
Fujino
Masayuki
M
Kitazawa
Yusuke
Y
Hara
Yuko
Y
Hara
Yoshiaki
Y
Hayakawa
Kou
K
Okuyama
Torayuki
T
Kimura
Hiromitus
H
Li
Xiao-Kang
XK
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
D018076:DNA, Complementary; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014366:Tryptophan Oxygenase