Impact of vaccine therapy using nuclear histone H1 on allograft survival in experimental organ transplantation.
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)-gamma 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.
Nakano
Toshiaki
T
Liver Transplantation Program and Department of Surgery, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, 123 Ta-Pei Rd., Niao-Sung, Kaohsiung 833, Taiwan.
Goto
Shigeru
S
Lai
Chia-Yun
CY
Hsu
Li-Wen
LW
Ono
Kazuhisa
K
Kawamoto
Seiji
S
Lin
Yu-Chun
YC
Kao
Ying-Hsien
YH
Chiang
Kuei-Chen
KC
Ohmori
Naoya
N
Goto
Takeshi
T
Sato
Shuji
S
Tu
Chieh-Hsien
CH
Jawan
Bruno
B
Cheng
Yu-Fan
YF
Chen
Chao-Long
CL
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006657:Histones / Q000276:immunology*; D007108:Immune Tolerance; D007150:Immunohistochemistry; D016233:Immunotherapy, Active; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D001323:Autoantibodies; D016207:Cytokines; D006657:Histones