title: Liver transplantation-induced antihistone H1 autoantibodies suppress mixed lymphocyte reaction.
abstract: BACKGROUND
  In a rat model of orthotopic liver transplantation (OLT), recipient serum after OLT (post-OLT serum) has been reported to prevent allograft rejection. However, the molecular identities of immunosuppressive factors, which are in the early stage of post-OLT, remain elusive. This study was aimed to identify immunodominant suppressive factors present in early post-OLT serum.
  
  
  METHODS
  The immunosuppressive activities of post-OLT serum, immunoglobulin (Ig) G-depleted serum, and purified IgG were evaluated in vitro by inhibition of the mixed lymphocyte reaction (MLR). Autoantigens recognized by the MLR-inhibitory IgG in early post-OLT serum were identified by the internal protein sequencing.
  
  
  RESULTS
  Recipient post-OLT serum inhibited MLR, and its immunosuppressive activity vanished by means of the elimination of OLT-inducible IgG. IgG from post-OLT sera (2-3 weeks) specifically reacted to 31-, 34-, and 73-kDa autoantigens on splenic cells. The internal sequences of the doublet 31- and 34-kDa antigens coincided completely with those of histone H1 molecules. The levels of histone H1-specific antibodies were transiently increased to a plateau around 2 to 3 weeks after OLT but decreased in the later tolerogenic phase. Immunodepletion of antihistone H1 autoantibodies from early post-OLT serum abolished the MLR-inhibitory activity. Furthermore, rabbit polyclonal antibody-directed histone H1 not only suppressed MLR but also prolonged allograft survival.
  
  
  CONCLUSIONS
  In this article, the authors provide evidence that autoreactive antibodies against histone H1, which are transiently induced at the early stage by liver transplantation, are a major OLT-induced graft survival factor.
authors.affiliation: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lai
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sasaki
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Aki
authors.forename: Seiko
authors.initials: S
authors.lastname: Shigeta
authors.forename: Takeshi
authors.initials: T
authors.lastname: Goto
authors.forename: Shuji
authors.initials: S
authors.lastname: Sato
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ono
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D001324:Autoantigens / Q000276:immunology; D003429:Cross Reactions; D006657:Histones / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016031:Liver Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000954:Antigens, Surface; D001323:Autoantibodies; D001324:Autoantigens; D006657:Histones; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents