title: Impact of vaccine therapy using nuclear histone H1 on allograft survival in experimental organ transplantation.
abstract: BACKGROUND
  We recently reported that autoreactive antibody (Ab) against nuclear histone H1 had been identified as an immunosuppressive factor in a rat tolerogenic orthotopic liver transplantation (OLT) model. The present study aimed to determine whether the up-regulation of antihistone H1 Ab by histone H1 vaccination leads to tolerance.
  
  
  METHODS
  Histone H1-immunized rats were established by intraperitoneal vaccination with histone H1 at every two-weekly interval. By using mixed lymphocyte reaction (MLR) and heterotopic heart transplantation (HHT), the alloreactive T cell response and allograft survival of histone H1-immunized rats were compared with those of control rats. Cytokine and cellular profiles in histone H1-immunized rats were determined by reverse transcriptase polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and flow cytometry.
  
  
  RESULTS
  Immunization with histone H1 in Freund's adjuvant induced alloreactive T cell unresponsiveness and prolonged heterotopic heart allograft survival. It also down-regulated the expression of major histocompatibility complex (MHC) class II and CD25 on splenic cells, elevated the T helper cell type 2 (Th2) skewing index (Interleukin (IL)-4/interferon (IFN)-gamma ratio or IL-4/IL-2 ratio) and modified the serum cytokine profiles.
  
  
  CONCLUSIONS
  The present results suggest that histone H1 vaccination of transplant recipients, which leads to the production of immunosuppressive factor and the modification of the cytokine/cellular profiles, has great potential as a tolerance therapy for prospective transplantation.
authors.affiliation: Liver Transplantation Program and Department of Surgery, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, 123 Ta-Pei Rd., Niao-Sung, Kaohsiung 833, Taiwan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lai
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Hsu
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ono
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Kuei-Chen
authors.initials: KC
authors.lastname: Chiang
authors.forename: Naoya
authors.initials: N
authors.lastname: Ohmori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Goto
authors.forename: Shuji
authors.initials: S
authors.lastname: Sato
authors.forename: Chieh-Hsien
authors.initials: CH
authors.lastname: Tu
authors.forename: Bruno
authors.initials: B
authors.lastname: Jawan
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Cheng
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006657:Histones / Q000276:immunology*; D007108:Immune Tolerance; D007150:Immunohistochemistry; D016233:Immunotherapy, Active; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D006657:Histones