Both investigators contributed equally.
Gene delivery of indoleamine 2,3-dioxygenase prolongs cardiac allograft survival by shaping the types of T-cell responses
Version of Record online: 2 MAY 2008
Copyright © 2008 John Wiley & Sons, Ltd.
The Journal of Gene Medicine
Volume 10, Issue 7, pages 754–761, July 2008
How to Cite
Yu, G., Dai, H., Chen, J., Duan, L., Gong, M., Liu, L., Xiong, P., Wang, C.-Y., Fang, M. and Gong, F. (2008), Gene delivery of indoleamine 2,3-dioxygenase prolongs cardiac allograft survival by shaping the types of T-cell responses. J. Gene Med., 10: 754–761. doi: 10.1002/jgm.1201
- Issue online: 16 JUN 2008
- Version of Record online: 2 MAY 2008
- Manuscript Accepted: 26 MAR 2008
- Manuscript Revised: 25 MAR 2008
- Manuscript Received: 5 DEC 2007
- adenovirus vector;
- indoleamine 2,3-dioxygenase;
- gene delivery;
We investigated the hypothesis that overexpression of indoleamine 2,3-dioxygenase (IDO) by a cardiac allograft may result in a survival advantage of the allograft by creating a tolerogenic microenvironment.
An adenoviral vector encoding for murine IDO cDNA (AdIDO) was transfected into murine allogeneic cardiac allografts, and transplantation was performed for evaluation of the effects of local AdIDO transfection on allograft survival. Intragraft IDO expression and lymphocytes infiltration were measured by immunohistochemical and histological analysis. Quantitative polymerase chain reaction assays, mixed lymphocyte reaction and flow cytometric analysis were employed to determine the expression of mRNA for Foxp3, IDO, pro-inflammatory cytokines, allogeneic T-cell proliferation and the proportion of CD4+CD25+Foxp3+ regulatory T cells (Tregs) from graft-infiltrating lymphocytes and splenocytes of recipients, respectively.
Cardiac allografts transfected with AdIDO showed a significant prolonged survival compared to the control groups. Hearts treated with AdIDO exhibited considerable up-regulation of IDO expression, whereas contained significantly reduced transcript levels for interleukin (IL)-2, interferon-γ and IL-17. These T cells isolated from allografts pre-treated with AdIDO displayed a dramatic reduction of proliferation capacity to alloantigen stimuli and had a significant higher proportion of Tregs compared to the control, as demonstrated by an increase of Foxp3 expression in allografts pre-treated with AdIDO compared to control groups.
Overexpression of IDO significantly delays cardiac allograft acute rejection by shaping the types of T-cell responses elicited by alloantigen stimuli. Copyright © 2008 John Wiley & Sons, Ltd.