Lee K, Hacker H, Umansky V, Schirrmacher V, Rocha M
DEUTSCH KREBSFORSCHUNGSZENTRUM,ZELLULARE IMMUNOL ABT,FSP TUMORIMMUNOL,D-69120 HEIDELBERG,GERMANY. DEUTSCH KREBSFORSCHUNGSZENTRUM,EXPT PATHOL ABT,FSP KREBSRISKIKOFAKTOREN & KREBSPRAVENT,D-6900 HEIDELBERG,GERMANY.
Int J Oncol. 1996 Oct;9(4):635-43. doi: 10.3892/ijo.9.4.635.
We investigated the influence of transient graft-versus-leukemia (GvL) and graft-versus-host reactivity (GvH) following allogeneic immune cell transfer on the glycogen and lipid metabolism in the liver of affected mice to better understand the underlying mechanism of these phenomena. As model we used a well established adoptive cellular immunotherapy (ADI) system. This involves transfer of in situ activated anti-tumor immune spleen lymphocytes (ISPL) from the tumor-resistant mouse strain B10.D2 (H-2(d), M1s(b)) into 5 Gy sublethally irradiated syngeneic ESb-MP lymphoma-bearing DBA/2 (H-2(d), M1s(a)) mice. Experiments were performed by transfer of ISPL from B10.D2 into DBA/2 tumor-bearing mice (GvL effect on liver metabolism) and into DBA/2 non-tumor-bearing mice (GvH effect on liver metabolism). Our results show that glycogen in hepatocytes decreased dramatically 5 days after ISPL transfer, which coincided with a high increase of large fat granules. 8 days after ISPL transfer, livers started to re-express glycogen and to decrease their lipid content. Normalization of both parameters was seen after day 30. These changes were qualitatively similar in both GvL and GvH. Measurement of activity of the liver marker enzymes, GOT and GPT, in the sera of animals subjected to GvL or GvH, showed peak values also at day 5, coinciding with the loss of glycogen. Quantitative differences were seen, however, in that much higher levels were reached in GvL than in GvH. Immune system recovery from irradiation damage and liver regeneration after immune cell mediated liver damage are likely explanations for the reversibility of the metabolic changes and for the lack of GVH disease and mortality in this new and effective cellular cancer immunotherapy model.
我们研究了异基因免疫细胞转移后短暂的移植物抗白血病（GvL）和移植物抗宿主反应（GvH）对受影响小鼠肝脏中糖原和脂质代谢的影响，以更好地理解这些现象的潜在机制。作为模型，我们使用了一个成熟的过继性细胞免疫疗法（ADI）系统。这涉及将来自抗瘤小鼠品系B10.D2（H-2(d)，M1s(b)）的原位活化抗肿瘤免疫脾淋巴细胞（ISPL）转移到经5 Gy亚致死剂量照射的同基因ESb-MP淋巴瘤荷瘤DBA/2（H-2(d)，M1s(a)）小鼠体内。实验通过将ISPL从B10.D2转移到荷瘤DBA/2小鼠（GvL对肝脏代谢的影响）和非荷瘤DBA/2小鼠（GvH对肝脏代谢的影响）中来进行。我们的结果表明，ISPL转移后5天，肝细胞中的糖原急剧减少，这与大脂肪颗粒的大量增加同时发生。ISPL转移后8天，肝脏开始重新表达糖原并降低其脂质含量。30天后观察到这两个参数均恢复正常。这些变化在GvL和GvH中在性质上相似。在接受GvL或GvH的动物血清中测量肝脏标志物酶GOT和GPT的活性，也在第5天出现峰值，与糖原的丧失同时发生。然而，存在定量差异，即GvL中的水平比GvH中的水平高得多。免疫系统从辐射损伤中恢复以及免疫细胞介导的肝脏损伤后的肝脏再生可能是代谢变化可逆性以及在这种新的有效细胞癌症免疫疗法模型中缺乏GVH疾病和死亡率的原因。
