Impact of vaccine therapy using nuclear histone H1 on allograft survival in experimental organ transplantation

Toshiaki Nakano, Shigeru Goto, Chia Yun Lai, Li Wen Hsu, Kazuhisa Ono, Seiji Kawamoto, Yu Chun Lin, Ying Hsien Kao, Kuei Chen Chiang, Naoya Ohmori, Takeshi Goto, Shuji Sato, Chieh Hsien Tu, Bruno Jawan, Yu Fan Cheng, Chao Long Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

11 Scopus citations


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)-γ 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.

Original languageEnglish
Pages (from-to)147-152
Number of pages6
JournalTransplant Immunology
Issue number3
StatePublished - 04 2007
Externally publishedYes


  • Anti-histone H1 autoantibody
  • Histone H1
  • Th1/Th2 balance
  • Tolerance induction
  • Vaccine


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