title: Gene delivery of indoleamine 2,3-dioxygenase prolongs cardiac allograft survival by shaping the types of T-cell responses.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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-gamma 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.
  
  
  CONCLUSIONS
  Overexpression of IDO significantly delays cardiac allograft acute rejection by shaping the types of T-cell responses elicited by alloantigen stimuli.
authors.affiliation: Department of Immunology, Laboratory of Transplantation, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yu
authors.forename: Hong
authors.initials: H
authors.lastname: Dai
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Lihua
authors.initials: L
authors.lastname: Duan
authors.forename: Min
authors.initials: M
authors.lastname: Gong
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Xiong
authors.forename: Cong-Yi
authors.initials: CY
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.forename: Feili
authors.initials: F
authors.lastname: Gong
mesh_terms: D000256:Adenoviridae; D000818:Animals; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006085:Graft Survival / Q000235:genetics*; D016027:Heart Transplantation / Q000276:immunology / Q000379:methods*; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016038:Skin Transplantation / Q000379:methods; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D018076:DNA, Complementary; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase