Yoshimura N, Ohsaka Y, Hamashima T, Yura H, Yasuii H, Oka T
Second Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Eur Surg Res. 1997;29(2):116-23. doi: 10.1159/000129515.
Our previous study demonstrated that Lewis (LEW) rat recipients engrafted with Brown-Norway (BN) rat liver displayed a long-term graft survival and that phenotypic and functional analyses of graft-infiltrating cells on day 6 postgrafting showed a lower proportion and activity of cytotoxic cells in long-term surviving hosts than LEW recipients engrafted with DA rat liver which showed acute rejection on day 9 postgrafting. In order to assess the immunological mechanisms of unresponsiveness, we analyzed the lymphocyte and serum from LEW recipients engrafted with BN liver. Spleen cells from tolerant LEW recipients on day 6 posttransplantation had no suppressor effect on the one-way mixed lymphocyte culture (MLC) reaction. On the other hand, when serum was added to MLC at a concentration of 6% of the total volume, it suppressed the mixed lymphocyte reaction (MLR) toward donor BN cells by 45.6%, but not toward third-party DA stimulator (-0.4%). Adoptive transfer of the serum from tolerant LEW hosts into the virgin secondary LEW hosts significantly prolonged the graft survival of BN kidneys from 7.8 +/- 0.2 to 14.7 +/- 1.6 days (p < 0.01), but not of third party DA kidney graft (mean survival time = 9.5 +/- 1.3 days). The in vitro study demonstrated that the suppressor factor in the serum inhibited the production of IL-2 as well as gamma-IFN in MLR. The suppressor factor was absorbed by LEW cells stimulated with BN cells in vitro, indicating that this factor was directed against recognition sites on responder T lymphocytes. These results showed that an antigen-specific tolerogenic factor which recognized the idiotype of the donor was released into the circulation through the process of BN liver grafting.
我们先前的研究表明，移植了布朗-挪威（BN）大鼠肝脏的刘易斯（LEW）大鼠受体显示出长期的移植物存活，并且在移植后第6天对移植物浸润细胞进行的表型和功能分析表明，与移植了DA大鼠肝脏且在移植后第9天出现急性排斥反应的LEW受体相比，长期存活宿主中细胞毒性细胞的比例和活性较低。为了评估无反应性的免疫机制，我们分析了移植了BN肝脏的LEW受体的淋巴细胞和血清。移植后第6天，耐受的LEW受体的脾细胞对单向混合淋巴细胞培养（MLC）反应没有抑制作用。另一方面，当以总体积的6%的浓度将血清添加到MLC中时，它抑制了对供体BN细胞的混合淋巴细胞反应（MLR）达45.6%，但对第三方DA刺激物没有抑制作用（-0.4%）。将耐受的LEW宿主的血清过继转移到未接触过抗原的二级LEW宿主中，显著延长了BN肾移植物的存活时间，从7.8±0.2天延长至14.7±1.6天（p<0.01），但对第三方DA肾移植物没有延长作用（平均存活时间=9.5±1.3天）。体外研究表明，血清中的抑制因子在MLR中抑制了IL-2以及γ-干扰素的产生。该抑制因子被体外经BN细胞刺激的LEW细胞吸收，表明该因子针对反应性T淋巴细胞上的识别位点。这些结果表明，一种识别供体独特型的抗原特异性致耐受性因子通过BN肝脏移植过程释放到循环中。
