Dendritic cells transfected with indoleamine 2,3-dioxygenase gene suppressed acute rejection of cardiac allograft

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Abstract

Background

Immunomodulation by indoleamine 2,3-dioxygenase (IDO) has been documented in many studies yet its underlying mechanisms remain undefined, especially in solid organ transplantation. Recent research demonstrated that the active expression of IDO in dendritic cells (DCs) regulates immune reaction. This study assessed whether DCs transfected with IDO gene inhibit T cells responses and suppress cardiac allograft rejection.

Methods

Adenovirus vector containing IDO gene was transfected into DCs to obtain IDO-positive DCs (IDO+ DCs). To evaluate the effect of IDO+ DCs on T cells in vitro, CD4+ T cell proliferation and apoptosis was assessed in mixed lymphocyte reactions and measured by flow cytometry, respectively. IDO+ DCs from C57BL/6 mice were injected into BALB/c recipients before heterotopic cardiac transplantation.

Results

Supernatant fluids from cultures of IDO+ DCs had decreased tryptophan and increased kynurenine levels, reflecting IDO activity. IDO+ DCs suppressed CD4+ T cell responses in vitro, as reflected by decreased proliferation and increased apoptosis. In the transplant model, IDO+ DCs prolonged survival and alleviated rejection of cardiac allograft in recipients injected with IDO+ DCs. In vivo, IDO+ DCs also significantly impaired CD4+ T cell responses promoting increased apoptosis and a Th2-dominant cytokine shift.

Conclusions

IDO overexpression in DCs suppressed T cells alloresponses in vitro, and IDO+ DCs attenuated acute allograft rejection in vivo. Regulation of tryptophan catabolism by means of IDO overexpression in DCs may be a useful approach in cardiac transplantation and immunological tolerance.

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