DEVELOPMENT OF LYMPHOMA IN THE THYMUS

我们建议继续我们对T细胞淋巴瘤生物学的研究 AKR小鼠。总体目标是更好地了解 在这种小鼠品系中发生的病毒和细胞相互作用 产生胸腺淋巴瘤。该计划建立在过去观察到的来自 该实验室和其他实验室，并提出了三种创新方法。 首先，我们展示了骨髓中的淋巴瘤前细胞。这些 细胞不能自主生长，但它们会成为淋巴瘤细胞 在它们迁移到胸腺之后。我们将研究这些细胞的表型。 细胞。他们将尝试在体外培养它们。这将是确定的 如果在体外感染克隆的AKR淋巴组织瘤病毒可以导致 淋巴瘤前细胞的表达。该提案的第二部分将 目的：研究淋巴组织源性病毒在小鼠体内的传播。 “无病毒”品系的小鼠(CBA/H和NFS)。某些克隆的分离株 对AKR株有促淋巴瘤作用的AKR病毒可诱导 胸腺淋巴瘤在这两个菌株中发生，而其他菌株没有，因此使 比较这些感兴趣病毒的器官(组织)表达。 在提案的第三部分，我们将研究淋巴瘤细胞系 他们对皮质类固醇的敏感性或抵抗力。对类固醇敏感和 从亲本AKR淋巴瘤细胞系中分离出耐药克隆。 含有正常数量激素受体的耐药细胞系 似乎是由于对激素敏感的体外分化所致 细胞。我们希望确定耐药细胞系是否可以在 敏感品系的体内接种及体内生长研究 这些线的属性。这两个细胞系也将用于 分子克隆类固醇基因的新实验方法 T细胞不同阶段表达不同的诱导裂解 差异化。

We propose to continue our studies of the biology of the T cell lymphoma in AKR mice. The overall aim is to develop a better understanding of the viral and cellular interactions which take place in this mouse strain to produce thymic lymphoma. The program is built on past observations from this and other laboratories and proposes three innovative approaches. First, we have demonstrated prelymphoma cells in the bone marrow. These cells are not capable of autonomous growth but they become lymphoma cells after they migrate to the thymus. We will study the phenotype of these cells. Attempts will be made to grow them in vitro. It will be determined if in vitro infection with cloned AKR lymphomagenic viruses can result in the expression of prelymphoma cells. A second part of this proposal will be to study the in vivo spread of lyphomagenic viruses in the tissues of 'virus free' strains of mice (CBA/H and NFS). Certain cloned isolates of the AKR viruses which are lymphoma-accelerating for the AKR strain induce thymic lymphoma in these two strains while others do not, thus, making a comparison of the organ (tissue) expression of these viruses of interest. In the third part of the proposal, we will study lymphoma cell lines for their sensitivity or resistance to corticosteroids. Steroid sensitive and resistant clones have been isolated from a parent AKR lymphoma cell line. The resistant cell line containing normal numbers of hormone receptors appears to result from an in vitro differentiation of the hormone sensitive cells. We wish to determine if resistant cells lines can be derived after in vivo inoculation of the sensitive lines and to study the in vivo growth properties of these lines. These two cell lines will also be used for a new experimental approach to molecularly clone the genes for steroid induced lysis which vary in their expression at different stages of T cell differentiation.