Hays E F, Bristol G
Laboratory of Biomedical and Environmental Sciences, Los Angeles, CA 90024-1786.
Thymus. 1992 Jun;19(4):219-34.
These studies were designed to look for a correlation of intrathymic survival of virus-infected thymocytes with lymphomagenesis. Cells from the normal-appearing prelymphoma thymus of SL3-3 virus-treated AKR mice were studied. Also, phenotypic properties of the malignant cells from the virus-induced lymphomas are described. In this model system, 100% of mice inoculated with virus at three days of age develop thymic lymphoma between 60 and 90 days of age. The experiments show that cells with malignant potential do not appear in the thymus until 36 days after virus inoculation. These cells are initially thymus-dependent (TD) in that they produce lymphoma of donor-type in recipients after intrathymic inoculation with long latency. They do not produce lymphoma after subcutaneous inoculation in syngeneic hosts. At 39 days after virus inoculation, the first thymus independent (TI) lymphoma cells appear. These cells, like the cells isolated from thymi with overt tumors, produce lymphoma of donor-type after a short latency when inoculated by the intrathymic or subcutaneous route. Thymocytes from normal-appearing thymi of mice at 42 days after virus inoculation, which could be expected to include TD, TI or no lymphoma cells, were evaluated for their ability to survive in a recipient thymus for three weeks after intrathymic inoculation. They were compared to thymocytes from age-matched control mice. Thymi receiving the virus-infected thymocytes showed 15% to 80% donor cells at three weeks. The highest numbers of donor cells were from thymi which were shown to contain TI lymphoma cells. However, cells from thymi with TD and no lymphoma cells could also be detected in significant numbers at three weeks after intrathymic inoculation. Less than 2% of donor-type thymocytes could be found after inoculation of thymocytes from normal control AKR mice. These data provide evidence that virus infection of thymocytes, even before the appearance of cells with lymphomagenic potential, endows them with a capacity for prolonged intrathymic survival. This appears to be a necessary step for tumor progression in this model. A remarkable phenotypic diversity of the virus-induced lymphomas was shown. The effect of various growth environments, intrathymic, subcutaneous, and in vitro on lymphoma cell phenotypic expression revealed individual differences in each tumor and in each environment.
这些研究旨在寻找病毒感染的胸腺细胞在胸腺内的存活与淋巴瘤发生之间的相关性。对经SL3 - 3病毒处理的AKR小鼠外观正常的淋巴瘤前期胸腺细胞进行了研究。此外，还描述了病毒诱导的淋巴瘤中恶性细胞的表型特征。在这个模型系统中，100%在3日龄接种病毒的小鼠在60至90日龄之间会发生胸腺淋巴瘤。实验表明，具有恶性潜能的细胞直到病毒接种后36天才出现在胸腺中。这些细胞最初依赖胸腺（TD），因为在胸腺内接种后，它们在受体中经过长时间潜伏期才产生供体类型的淋巴瘤。在同基因宿主中皮下接种后它们不会产生淋巴瘤。在病毒接种后39天，第一批不依赖胸腺（TI）的淋巴瘤细胞出现。这些细胞，就像从有明显肿瘤的胸腺中分离出的细胞一样，在通过胸腺内或皮下途径接种后，经过短暂潜伏期就会产生供体类型的淋巴瘤。对病毒接种后42天外观正常的小鼠胸腺细胞进行评估，预期这些细胞包括TD、TI或无淋巴瘤细胞，评估它们在胸腺内接种后在受体胸腺中存活三周的能力。将它们与年龄匹配的对照小鼠的胸腺细胞进行比较。接受病毒感染的胸腺细胞的胸腺在三周时显示15%至80%的供体细胞。供体细胞数量最多的来自显示含有TI淋巴瘤细胞的胸腺。然而，在胸腺内接种三周后，也能大量检测到来自含有TD但无淋巴瘤细胞的胸腺的细胞。接种正常对照AKR小鼠的胸腺细胞后，发现不到2%的供体类型胸腺细胞。这些数据证明，即使在具有淋巴瘤发生潜能的细胞出现之前，胸腺细胞的病毒感染就赋予了它们在胸腺内长期存活的能力。在这个模型中，这似乎是肿瘤进展的一个必要步骤。研究显示病毒诱导的淋巴瘤具有显著的表型多样性。各种生长环境（胸腺内、皮下和体外）对淋巴瘤细胞表型表达的影响揭示了每个肿瘤和每种环境中的个体差异。
