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Current Trends in Immunology   Volumes    Volume 12 
Abstract
Autoimmunity and liver transplantation immunology
Shigeru Goto, Toshiaki Nakano, Li-Wen Hsu, Kuei-Chen Chiang, Chia-Yun Lai, Seiji Kawamoto, Kazuhisa Ono, Kuang-Den Chen, Naoya Ohmori, Takeshi Goto, Shuji Sato, Yur-Ren Kuo, Chih-Chi Wang, Bruno Jawan, Yu-Fan Cheng, Chao-Long Chen
Pages: 1 - 11
Number of pages: 11
Current Trends in Immunology
Volume 12 

Copyright © 2011 Research Trends. All rights reserved

ABSTRACT
 
Recent proteomic approach allows us to target on specific molecules underlying the common mechanism between experimental and clinical liver allograft tolerance. Especially, new insight has been gained from our studies since we found that post-transplant autoimmune responses with high titer of anti-nuclear antibodies against histone H1 and high mobility group box 1 (HMGB1) play an important role in the induction of liver allograft tolerance in OLT rats and clinical drug-free OLT patients. Our previous studies showed that either treatment of recipient rats with commercially available histone H1 polyclonal Ab or immunization with calf thymus histone H1 could prolong allograft survival in heterotopic heart transplantation. We have also reported that the blockade of histone H1 modulated dendritic cells toward tolerogenic status, decreased the cytotoxicity of lymphokine activated killer and natural killer cells, and induced CD4+CD25+ T-cells. For further analysis of this mechanism, we generated an immunosuppressive histone H1 monoclonal Ab (16G9 mAb) and determined one peptide (designated SSV) that binds directly to 16G9 mAb. The binding of SSV to 16G9 mAb or serum of both tolerogeneic OLT rats and clinical drug-free OLT patients, was inhibited by histone H1. Furthermore, immunization of mice with SSV induced immunosuppression in serum, suggesting that SSV was an epitope responsible for the immunosuppressive activity of 16G9 mAb. 16G9 mAb and peptide SSV will allow us to establish a novel diagnostic and therapeutic strategy in transplantation. This article reviews our work exploring how the autoimmune response against nuclear proteins is involved in liver transplantation immunology.
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