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J Gene Med. 2005 May;7(5):565-75.

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

Author information

1
Laboratory of Transplantation Immunology, Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan.

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.

PMID:
15543532
DOI:
10.1002/jgm.698
[Indexed for MEDLINE]

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