Dendritic cells transfected with indoleamine 2,3-dioxygenase gene suppressed acute rejection of cardiac allograft.
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.
Department of General Surgery, Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District,Tianjin 300052, China. Electronic address: lichuan1980@hotmail.com.
Chuan
C
Li
Department of General Surgery, Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District,Tianjin 300052, China. Electronic address: liutonga@126.com.
Tong
T
Liu
Department of General Surgery, Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District,Tianjin 300052, China. Electronic address: nasy3367@126.com.
Na
N
Zhao
Department of General Surgery, Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District,Tianjin 300052, China. Electronic address: zhuliwei0804@126.com.
Liwei
L
Zhu
Department of General Surgery, Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District,Tianjin 300052, China. Electronic address: wangpz2009@gmail.com.
Pengzhi
P
Wang
Department of General Surgery, Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District,Tianjin 300052, China. Electronic address: mzzlee@163.com.
Xiangchen
X
Dai
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology / Q000637:transplantation*; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase
Cardiac transplantation; Dendritic cells; Immunological tolerance; Indoleamine 2,3-dioxygenase; Rejection