Nakano Toshiaki, Goto Shigeru, Lai Chia-Yun, Hsu Li-Wen, Wong Jin-Long, Kawamoto Seiji, Chiang Kuei-Chen, Ohmori Naoya, Goto Takeshi, Sato Shuji, Yang Chin-Hsiang, Wang Chih-Chi, Jawan Bruno, Cheng Yu-Fan, Ono Kazuhisa, Chen Chao-Long
Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Transpl Immunol. 2008 May;19(2):87-92. doi: 10.1016/j.trim.2008.04.001. Epub 2008 May 1.
Our recent studies suggested that anti-histone H1 autoantibody (auto-Ab) plays an important role in experimental and clinical liver allograft tolerance as a natural immunosuppressive factor. The present study aimed to explore how the autoimmune response against histone H1 is involved in tolerance induction.
The measurement of anti-histone H1 auto-Ab and immunohistochemical analysis were performed in serum and liver allografts after orthotopic liver transplantation (OLT). To compare the auto-Ab response against histone H1 between the recipients of rejector (DA-LEW) and tolerogenic (DA-PVG) OLT models, naïve recipients were immunized with calf thymus histone H1. The immunosuppressive state of histone H1-immunized rats was assayed by mixed lymphocyte reaction (MLR).
Anti-histone H1 Ab titer was transiently increased during the rejection phase after OLT (days 7-21) in the DA-PVG combination, while no such response was confirmed in the DA-LEW acute rejection model. Nuclear histone H1 antigens were found in the cytoplasm and the extracellular environment in liver allografts at the rejection phase in the tolerogenic model but not in the rejector model, resulting from the transient induction of anti-histone H1 auto-Ab in recipient PVG rats after OLT. Low dose and short-term immunization with histone H1 upregulated the anti-histone H1 Ab titer in naïve PVG rats, which exhibited a low allogeneic immune response, while no such response was found in naïve LEW rats.
These results suggest that the sensitivity to nuclear antigens such as histone H1 may be a key factor determining the acceptance or rejection of donor liver grafts, at least in DA-PVG and DA-LEW combinations.
我们最近的研究表明，抗组蛋白H1自身抗体（自身抗体）作为一种天然免疫抑制因子，在实验性和临床肝移植耐受中发挥重要作用。本研究旨在探讨针对组蛋白H1的自身免疫反应如何参与耐受诱导。
在原位肝移植（OLT）后，对血清和肝移植组织进行抗组蛋白H1自身抗体的检测及免疫组化分析。为比较排斥组（DA-LEW）和耐受组（DA-PVG）OLT模型受体针对组蛋白H1的自身抗体反应，将未接触过抗原的受体用小牛胸腺组蛋白H1免疫。通过混合淋巴细胞反应（MLR）检测组蛋白H1免疫大鼠的免疫抑制状态。
在DA-PVG组合中，OLT后排斥期（第7 - 21天）抗组蛋白H1抗体滴度短暂升高，而在DA-LEW急性排斥模型中未证实有此类反应。在耐受模型的排斥期，肝移植组织的细胞质和细胞外环境中发现了核组蛋白H1抗原，而在排斥组模型中未发现，这是由于OLT后受体PVG大鼠中抗组蛋白H1自身抗体的短暂诱导所致。用组蛋白H1低剂量短期免疫上调了未接触过抗原的PVG大鼠的抗组蛋白H1抗体滴度，其表现出低同种异体免疫反应，而在未接触过抗原的LEW大鼠中未发现此类反应。
这些结果表明，至少在DA-PVG和DA-LEW组合中，对组蛋白H1等核抗原的敏感性可能是决定供体肝移植接受或排斥的关键因素。
