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

✍ Scribed by Naoko Funeshima; Masayuki Fujino; Yusuke Kitazawa; Yuko Hara; Yoshiaki Hara; Kou Hayakawa; Torayuki Okuyama; Hiromitus Kimura; Xiao-Kang Li

Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
222 KB
Volume
7
Category
Article
ISSN
1099-498X

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✦ Synopsis

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‐2^k^), 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‐2^b^) 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. Copyright © 2004 John Wiley & Sons, Ltd.

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