title: Characterization of immunosuppressive factors expressed in serum by rat tolerogenic liver transplantation.
abstract: BACKGROUND
  In a rat tolerogenic model of orthotopic liver transplantation (OLT), recipient serum after OLT (post-OLT serum) possesses strong immunosuppressive activity. This study aimed to identify immunosuppressive factors present in early post-OLT serum.
  
  
  METHODS
  Immunosuppressive activity was evaluated in vitro by inhibition of the mixed-lymphocyte reaction (MLR). Autoantigens recognized by MLR-inhibitory IgG were identified by the internal protein sequencing.
  
  
  RESULTS
  Recipient post-OLT serum inhibited MLR, and OLT-inducible IgG was the major immunosuppressive factor. IgG from post-OLT sera (2 to 3 weeks) specifically reacted to 31; 34; and 73-kd autoantigens on spleen cells. The internal sequences of the 31- and 34-kd antigens coincided completely with those of histone H1 molecules. Immunodepletion of anti-histone H1 antibodies (Abs) from early post-OLT serum abolished the MLR-inhibitory activity. Furthermore, rabbit polyclonal Ab-directed histone H1 not only significantly suppressed rat and human MLR but also prolonged survival of heart allografts. Flow-cytometric analysis revealed that some live PVG splenocytes were stained with antihistone H1 Abs, and that these positive cells increased on Con A stimulation. Western blot analysis indicated that several cross-reactive antigens against anti-histone H1 Abs were found in their membrane fraction.
  
  
  CONCLUSIONS
  In this study we provide evidence that autoreactive Abs, against histone H1 are a major OLT-induced graft survival factor, and may play at least a part in overcoming the acute rejection phase to establish solid allograft tolerance.
authors.affiliation: Department of Surgery, Liver Transplantation Laboratory, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: T
authors.initials: T
authors.lastname: Nakano
authors.forename: S
authors.initials: S
authors.lastname: Kawamoto
authors.forename: C-Y
authors.initials: CY
authors.lastname: Lai
authors.forename: L-W
authors.initials: LW
authors.lastname: Hsu
authors.forename: Y-C
authors.initials: YC
authors.lastname: Lin
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Aki
authors.forename: S
authors.initials: S
authors.lastname: Shigeta
authors.forename: T
authors.initials: T
authors.lastname: Goto
authors.forename: N
authors.initials: N
authors.lastname: Ohmori
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Goto
authors.forename: K
authors.initials: K
authors.lastname: Ono
authors.forename: C-L
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006657:Histones / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods*; D016031:Liver Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D023421:Models, Animal; D018448:Models, Immunological; D051381:Rats; D013154:Spleen / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D001324:Autoantigens; D006657:Histones; D007074:Immunoglobulin G