DEVELOPMENT OF LYMPHOMA IN THE THYMUS

我们建议继续研究T细胞淋巴瘤的生物学， AKR小鼠。 总体目标是更好地了解 病毒和细胞的相互作用发生在这种小鼠品系， 产生胸腺淋巴瘤。 该计划是建立在过去的观察， 这个实验室和其他实验室，并提出了三个创新的方法。 首先，我们已经证明了骨髓中的前淋巴瘤细胞。 这些 细胞不能自主生长，但它们会变成淋巴瘤细胞 在它们迁移到胸腺后。 我们将研究这些基因的表型 细胞 将尝试在体外培养它们。 将确定 如果体外感染克隆的AKR淋巴瘤病毒可以导致 淋巴瘤前细胞的表达。 该提案的第二部分将 研究致淋巴瘤病毒在组织中的体内传播， “无病毒”小鼠品系（CBA/H和NFS）。 某些克隆的 对AKR株具有淋巴瘤加速作用的AKR病毒诱导 胸腺淋巴瘤在这两个菌株，而其他人没有，因此， 这些感兴趣的病毒的器官（组织）表达的比较。 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性。 类固醇敏感， 抗性克隆已经从亲本AKR淋巴瘤细胞系中分离出来。 含有正常数量激素受体的耐药细胞系 似乎是由激素敏感性细胞的体外分化引起的。 细胞 我们希望确定是否可以在以下条件下获得抗性细胞系： 体内接种敏感品系并研究体内生长 这些线的属性。 这两种细胞系也将用于 分子克隆类固醇基因的新实验方法 诱导裂解，其在T细胞的不同阶段表达不同 分化

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.