Cornelius E A
J Exp Med. 1972 Dec 1;136(6):1533-44. doi: 10.1084/jem.136.6.1533.
When weanling (SJL/J x C57BL/1)F(1) hybrid mice were given five weekly-injections of small doses of viable SJL/J spleen cells, so as to induce a graft-versus-host reaction (GVHR), reticulum cell sarcomas were induced in all of the host mice by the 40th day after the first cell injection. Such tumors, on transplantation, were accepted by syngeneic (SJL/J x C57BL/1)F(1) and C57BL/1 hosts, but not by SJL/J or NZB mice. Cell-free extracts of SJL/J spleens injected into similar hybrids resulted in identical tumors in all hosts within the same period; the transplantation characteristics were also similar. Normal (SJL/J x C57BL/1)F(1) hybrids as well as similar hybrids injected with SJL/J liver or syngeneic F(1) spleen cells did not develop tumors. Cell-free preparations of eight tumors induced in F(1)'s by viable SLJ/J spleen cells were injected into newborn (C57BL/1 x A)F(1) and C57BL/1 mice: tumors were induced, with seven of eight tumor preparations, with a latent period of 33-49 days. Such tumors were lymphosarcomas, and, in the case of (C57BL/1 x A)F(1) hosts, further transplantation revealed that they were antigenically C57BL/1 tumors. These experiments provide conclusive evidence for a viral etiology of GVHR-induced tumors. Furthermore, tumor induction in the GVHR does not appear to depend specifically on an immunological mechanism but is most probably due to release or activation of a sufficient quantity of oncogenic virus within a certain time period in a highly susceptible host. Comparison with radiation induction of viral leukemia in mice revealed similarities in regard to optimal host age and the spacing of administration of the tumor-inducing agent. SJL/J mice carry a type C virus which causes a high incidence of spontaneous Hodgkin-like tumors by 1 yr of age; C57BL/1 mice do not develop lymphomas spontaneously but carry a latent leukemogenic virus. Their hybrid also has a low incidence of spontaneous lymphomas. Based on the results of these and previous experiments, the viruses of these strains of mice appear to be highly synergistic in tumor induction in the GVHR. The SJL/J virus is a powerful oncogenic agent. The C57BL/1 virus may be a helper virus to the SJL/J, but is a more powerful determinant of the antigenic composition of the induced tumors. This suggests that the virus of C57BL/1 mice, when activated, is capable of controlling the C57BL/1 genome. Because of the ease and rapidity of viral tumor induction, the SJL/J and C57BL/1 strains of mice, with their F(1) hybrid, should be useful for further study of the mechanisms controlling induction of such tumors.
给断奶的（SJL/J×C57BL/1）F1杂种小鼠每周注射小剂量活的SJL/J脾细胞，共注射5次，以诱导移植物抗宿主反应（GVHR）。在首次注射细胞后的第40天，所有宿主小鼠均诱发了网状细胞肉瘤。此类肿瘤移植时，能被同基因的（SJL/J×C57BL/1）F1和C57BL/1宿主接受，但不能被SJL/J或NZB小鼠接受。将SJL/J脾的无细胞提取物注射到类似的杂种小鼠体内，在同一时期内所有宿主均诱发了相同的肿瘤；其移植特性也相似。正常的（SJL/J×C57BL/1）F1杂种小鼠以及注射了SJL/J肝脏或同基因F1脾细胞的类似杂种小鼠均未发生肿瘤。将由活的SJL/J脾细胞在F1小鼠中诱发的8个肿瘤的无细胞制剂注射到新生的（C57BL/1×A）F1和C57BL/1小鼠体内：8种肿瘤制剂中的7种诱发了肿瘤，潜伏期为33 - 49天。此类肿瘤为淋巴肉瘤，对于（C57BL/1×A）F1宿主而言，进一步移植表明它们是抗原性为C57BL/1的肿瘤。这些实验为GVHR诱导的肿瘤的病毒病因提供了确凿证据。此外，GVHR中的肿瘤诱发似乎并非特别依赖于免疫机制，而很可能是由于在高度易感宿主中在一定时间段内释放或激活了足够数量的致癌病毒。与小鼠中病毒白血病的辐射诱导相比较，发现在最佳宿主年龄和肿瘤诱导剂给药间隔方面存在相似之处。SJL/J小鼠携带一种C型病毒，到1岁时会导致自发霍奇金样肿瘤的高发病率；C57BL/1小鼠不会自发发生淋巴瘤，但携带一种潜伏的致白血病病毒。它们的杂种自发淋巴瘤的发病率也较低。基于这些及先前实验的结果，这些品系小鼠的病毒在GVHR的肿瘤诱导中似乎具有高度协同作用。SJL/J病毒是一种强大的致癌剂。C57BL/1病毒可能是SJL/J病毒的辅助病毒，但在诱导肿瘤的抗原组成方面是更强大的决定因素。这表明C57BL/1小鼠的病毒激活后能够控制C57BL/1基因组。由于病毒诱导肿瘤简便快捷，SJL/J和C57BL/1品系小鼠及其F1杂种对于进一步研究控制此类肿瘤诱导的机制应是有用的。
