title: Histone H1 vaccine therapy for overcoming acute rejection in experimental organ transplantation.
abstract: OBJECTIVE
  In a rat tolerogenic orthotopic liver transplantation (OLT) model, the recipient serum (post-OLT serum) shows strong immunosuppressive activity. In our previous reports, we suggested that autoreactive antibody (Ab) against histone H1 is a major immunosuppressive factor in this serum. The present study sought to determine whether up-regulation of anti-histone H1 Ab by histone H1 vaccination led to tolerance.
  
  
  METHODS
  Using mixed lymphocyte reactions (MLR) and heterotopic heart transplantations (HHT), the alloreactive T-cell responses and allograft survivals of histone H1-immunized rats were compared with those of control rats. Cytokine and cellular profiles were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry.
  
  
  RESULTS
  The alloreactive T-cell response of histone H1-immunized rats was significantly lower than that of control rats, although there was no difference in nonspecific T-cell activation between the 2 groups. The allograft survival of histone H1-immunized rats was significantly prolonged after HHT. The major histocompatibility complex (MHC) class II and CD25 molecules of histone H1-immunized rats were significantly down-regulated compared with those of control rats. Moreover, the serum cytokine profile was modified by the immunization with histone H1.
  
  
  CONCLUSIONS
  These results suggest that histone H1 vaccination of transplant recipients leads to the production of immunosuppressive factors and the modification of cytokine/cellular profiles.
authors.affiliation: Chang Gung Memorial Hospital-Kaohsiung Medical Center, Department of Surgery, Kaohsiung, Taiwan.
authors.forename: T
authors.initials: T
authors.lastname: Nakano
authors.forename: K
authors.initials: K
authors.lastname: Ono
authors.forename: S
authors.initials: S
authors.lastname: Goto
authors.forename: C-Y
authors.initials: CY
authors.lastname: Lai
authors.forename: L-W
authors.initials: LW
authors.lastname: Hsu
authors.forename: S
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Y-C
authors.initials: YC
authors.lastname: Lin
authors.forename: Y-H
authors.initials: YH
authors.lastname: Kao
authors.forename: K-C
authors.initials: KC
authors.lastname: Chiang
authors.forename: N
authors.initials: N
authors.lastname: Ohmori
authors.forename: T
authors.initials: T
authors.lastname: Goto
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: B
authors.initials: B
authors.lastname: Jawan
authors.forename: Y-F
authors.initials: YF
authors.lastname: Cheng
authors.forename: C-L
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006657:Histones / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
chemical_list: D006657:Histones