title: Splenectomy increases the survival time of heart allograft via developing immune tolerance.
abstract: BACKGROUND
  The spleen is an active lymphoid organ. The effect of splenectomy on the immune response remains unclear. This study investigated whether splenectomy can induce immune tolerance and has a beneficial role in cardiac allograft.
  
  
  METHODS
  Wistar rats were used for heart donors. The Sprague-Dawley (SD) rats designated as the recipients of heart transplantation (HT) were randomly assigned into four groups: sham, splenectomy, HT, splenectomy + HT. The survival of transplanted hearts was assessed by daily checking of abdominal palpation. At various time points after transplantation, the transplanted hearts were collected and histologically examined; the level of CD4+CD25+ T regulatory lymphocytes (Tregs) and rate of lymphocyte apoptosis (annexin-v+ PI+ cells) in the blood were analyzed by using flow cytometric method.
  
  
  RESULTS
  1) Splenectomy significantly prolonged the mean survival time of heart allografts (7 ± 1.1 days and 27 ± 1.5 days for HT and splenectomy + HT, respectively; n = 12-14/group, HT vs. splenectomy + HT, p < 0.001); 2) Splenectomy delayed pathological changes (inflammatory cell infiltration, myocardial damage) of the transplanted hearts in splenectomy + HT rats; 3) The level of CD4+CD25+ Tregs in the blood of splenectomized rats was significantly increased within 7 days (2.4 ± 0.5%, 4.9 ± 1.3% and 5.3 ± 1.0% for sham, splenectomy and splenectomy + HT, respectively; n = 15/group, sham vs. splenectomy or splenectomy + HT, p < 0.05) after splenectomy surgery and gradually decreased to baseline level; 4) Splenectomy increased the rate of lymphocyte apoptosis (day 7: 0.3 ± 0.05%, 3.9 ± 0.9% and 4.1 ± 0.9% for sham, splenectomy and splenectomy + HT, respectively; n = 15/group, sham vs. splenectomy or splenectomy + HT, p < 0.05) in a pattern similar to the change of the CD4+CD25+ Tregs in the blood.
  
  
  CONCLUSIONS
  Splenectomy inhibits the development of pathology and prolongs the survival time of cardiac allograft. The responsible mechanism is associated with induction of immune tolerance via elevating CD4+CD25+ Tregs and increasing lymphocyte apoptosis.
authors.forename: Jinguo
authors.initials: J
authors.lastname: Zhu
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Chen
authors.forename: Jinju
authors.initials: J
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Ruilian
authors.initials: R
authors.lastname: Ma
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yao
mesh_terms: D064591:Allografts; D000818:Animals; D004195:Disease Models, Animal; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation; D007108:Immune Tolerance; D007111:Immunity, Cellular; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013156:Splenectomy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*