Induction of antinuclear antibodies by de novo autoimmune hepatitis regulates alloimmune responses in rat liver transplantation.
Concanavalin A (Con A) is a lectin originating from the jack-bean and well known for its ability to stimulate T cells and induce autoimmune hepatitis. We previously demonstrated the induction of immunosuppressive antinuclear autoantibody in the course of Con A-induced transient autoimmune hepatitis. This study aimed to clarify the effects of Con A-induced hepatitis on liver allograft rejection and acceptance. In this study, we observed the unique phenomenon that the induction of transient de novo autoimmune hepatitis by Con A injection paradoxically overcomes the rejection without any immunosuppressive drug and exhibits significantly prolonged survival after orthotopic liver transplantation (OLT). Significantly increased titers of anti-nuclear Abs against histone H1 and high-mobility group box 1 (HMGB1) and reduced donor specific alloantibody response were observed in Con A-injected recipients. Induction of Foxp3 and IL-10 in OLT livers of Con A-injected recipients suggested the involvement of regulatory T cells in this unique phenomenon. Our present data suggest the significance of autoimmune responses against nuclear histone H1 and HMGB1 for competing allogeneic immune responses, resulting in the acceptance of liver allografts in experimental liver transplantation.
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Liver Transplantation Program, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan.
Toshiaki
T
Nakano
Liver Transplantation Program, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Iwao Hospital, 3059-1 Kawakami, Yufu, Oita 879-5102, Japan.
Shigeru
S
Goto
Liver Transplantation Program, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Department of Veterinary Medicine, National Pingtung University of Science & Technology, 1 Shuehfu Road, Neipu, Pingtung 912, Taiwan.
Chia-Yun
CY
Lai
Liver Transplantation Program, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan.
Li-Wen
LW
Hsu
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Liver Transplantation Program, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan.
Hui-Peng
HP
Tseng
Liver Transplantation Program, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan.
Kuang-Den
KD
Chen
Liver Transplantation Program, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan.
King-Wah
KW
Chiu
Liver Transplantation Program, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan.
Chih-Chi
CC
Wang
Liver Transplantation Program, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan.
Yu-Fan
YF
Cheng
Liver Transplantation Program, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan ; Division of Transplant Immunology, Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan.
Chao-Long
CL
Chen
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D015551:Autoimmunity; D003208:Concanavalin A / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics; D006085:Graft Survival / Q000276:immunology; D024243:HMGB1 Protein / Q000097:blood / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D006657:Histones / Q000097:blood / Q000276:immunology; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D000974:Antibodies, Antinuclear; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D024243:HMGB1 Protein; D006657:Histones; D007518:Isoantibodies; D003208:Concanavalin A