title: Induction of CD4+CD25+ T cells and control of cardiac allograft rejection by CD40/CD40L costimulatory pathway blockade in mice.
abstract: BACKGROUND
  Rejection is a major problem in organ transplantation. We speculated that dendritic cells (DCs) with low expression of CD40 may inhibit T-cell responses providing protective effects on organ transplantions.
  
  
  METHODS
  RNA interference (RNAi) is an effective approach to degrade RNA levels of a target gene. We used RNAi to reduce CD40 levels in mouse bone marrow-derived DCs. Allogeneic T-lymphocyte proliferation stimulated by DCs was assessed in mixed lymphocyte reactions. A mouse model of heterotopic abdominal heart transplantation was performed to evaluate survival times and histologic grade of acute rejection at 7 days after transplantation. CD4(+)CD25(+) regulatory T cells (Tregs) in peripheral blood were quantified by flow cytometry.
  
  
  RESULTS
  Mouse DCs with reduced CD40 expression lowered the proliferation of recipient T cells. More DCs with silenced CD40 delayed cardiac allograft rejection.
  
  
  CONCLUSIONS
  Reduction of CD40 in DCs induced peripheral Tregs and delayed cardiac allograft rejection.
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China. fuweihua@tijmu.edu.cn
authors.forename: W
authors.initials: W
authors.lastname: Fu
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: Y
authors.initials: Y
authors.lastname: Qiu
authors.forename: W
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005434:Flow Cytometry; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D034622:RNA Interference; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D014162:Transfection
chemical_list: D019013:CD40 Antigens; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D023201:CD40 Ligand