title: Murine interleukin 4 transgenic heart allograft survival prolonged with down-regulation of the Th1 cytokine mRNA in grafts.
abstract: BACKGROUND
  Data supporting the differential activation of T helper (Th) 2 cells in transplantation acceptance/tolerance in rodents have been presented by several investigators. However, the differential activation of Th2 cells may be simply the result of allograft acceptance/tolerance induction instead of a contribution to the maintenance of grafts.
  
  
  METHODS
  Therefore, we established interleukin (IL)-4 transgenic mice under the control of a cardiac alpha-myosin heavy chain promotor and transplanted IL-4-expressing heart allografts into unmodified recipients to determine the actual contribution of the Th2 bias to allograft acceptance.
  
  
  RESULTS
  Among 16 newborn C57BL/6J (B6) mice, three were positive for the IL-4 transgene. Serum IL-4 levels of transgenic versus control B6xC3H F1 mice were not statistically different. Reverse-transcriptase polymerase chain reaction showed that the transgenic B6xC3H F1 mice expressed IL-4 mRNA in the heart and in the lung, whereas control mice did not express IL-4 in any organ. IL-4 mRNA expression in the transgenic but not in the control heart was also confirmed by RNAse protection assay and fluorescence in situ hybridization. The survival of IL-4 transgenic B6xC3H heart grafts heterotopically placed in C3H recipients was prolonged compared with that of nontransgenic grafts (19.0+/-9.1 vs. 6.8+/-2.2 days, P=0.003). Interferon-gamma mRNA expression in IL-4 transgenic heart grafts on the fifth posttransplant day as assessed by Northern blotting was suppressed compared with that in control grafts. Reverse-transcriptase polymerase chain reaction analysis showed that IL-2 mRNA was suppressed in the IL-4 transgenic grafts compared with that in control grafts, while IL-4 mRNA was observed only in IL-4 transgenic grafts. IL-10 mRNA was detected at similar levels in both transgenic and control grafts.
  
  
  CONCLUSIONS
  A Th2 bias may contribute to allograft acceptance in part by inducing the down-regulation of Th1-cytokine mRNAs, but it may not be sufficient to induce indefinite graft survival.
authors.affiliation: Department of Urology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Ueki
authors.forename: S
authors.initials: S
authors.lastname: Sunaga
authors.forename: K
authors.initials: K
authors.lastname: Ikuta
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: N
authors.initials: N
authors.lastname: Moriyama
authors.forename: J
authors.initials: J
authors.lastname: Miyazaki
authors.forename: K
authors.initials: K
authors.lastname: Kawabe
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006321:Heart / Q000033:anatomy & histology; D016027:Heart Transplantation / Q000276:immunology*; D015847:Interleukin-4 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000737:chemistry; D009218:Myosins / Q000235:genetics; D016612:Paraffin Embedding; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000737:chemistry; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D015847:Interleukin-4; D009218:Myosins