Mori Y, Mori T, Yoshida H, Ueda S, Iesato K, Wakashin Y, Wakashin M, Okuda K
Clin Exp Immunol. 1984 Jul;57(1):85-92.
This study was undertaken to produce experimental autoimmune hepatitis in mice, and to examine the role of liver specific lipoprotein (LSP), if any, and of cellular immunity in such a model. After immunization of three strains of mice (C57BL/6, C3H/He and BALB/c) with syngeneic crude liver proteins, most prominent liver changes histologically mimicking human hepatitis were produced in the liver of C57BL/6 (B6) mice. Antigenic and immunogenic activity of LSP in the crude liver proteins was decreased by the treatment of freezing and thawing, and the recovery of the antigenic activity seemed to correlate with the susceptibility of immunized mice to the induction of liver damage. Autoantibody against LSP was demonstrated in the serum of immunized B6 mice, but not in the sera of other strains after immunization. It was also found that EDTA contained in the buffer used for purification of LSP distinctly suppressed lymphocyte activity in vivo and in vitro. With the use of EDTA free LSP, it was shown that spleen cells of immunized B6 mice (especially of T cell enriched fraction) had a high reactivity studied by lymphocyte transformation test. Further examination showed that EDTA free LSP could induce mild liver lesions and lymphocyte reactivity against LSP, although neither histological change nor lymphocyte reactivity was found in the liver of B6 mice immunized with EDTA containing LSP.
本研究旨在诱导小鼠实验性自身免疫性肝炎,并在此模型中研究肝特异性脂蛋白(LSP)(若存在)及细胞免疫的作用。用同基因粗制肝蛋白免疫三种品系的小鼠(C57BL/6、C3H/He和BALB/c)后,C57BL/6(B6)小鼠肝脏出现了最显著的组织学变化,类似于人类肝炎。粗制肝蛋白中LSP的抗原性和免疫原性活性经冻融处理后降低,抗原活性的恢复似乎与免疫小鼠对肝损伤诱导的易感性相关。免疫后的B6小鼠血清中可检测到抗LSP自身抗体,而其他品系免疫后血清中未检测到。还发现,用于纯化LSP的缓冲液中所含的EDTA在体内和体外均能明显抑制淋巴细胞活性。使用不含EDTA的LSP时,通过淋巴细胞转化试验研究发现,免疫后的B6小鼠脾细胞(尤其是富含T细胞的部分)具有高反应性。进一步研究表明,不含EDTA的LSP可诱导轻度肝损伤以及针对LSP的淋巴细胞反应,而用含EDTA的LSP免疫的B6小鼠肝脏中未发现组织学变化和淋巴细胞反应。