Transplant Models

正如该项目的目标和目的所指出的，它旨在创造新的 这些模型检验了不同的假设，并为小说的发展提供了新的理解。 治疗淋巴瘤、骨髓瘤、白血病、乳腺癌和肾癌的策略， 造血干细胞移植造血干细胞移植治疗 疾病通常导致淋巴细胞减少症和免疫损害。观察到，在 在癌症的情况下， 治疗相关的淋巴细胞减少症已经转化为鼠模型。我们已经启动了四个 同时努力确定胸腺功能的控制点。在实验中， IGF-1，这是发现上调胸腺活动，我们观察到，而胸腺细胞 前体池的大小和参与迁移的分子受到影响， 点是在扩大成熟壁龛的水平传入胸腺细胞。停止 雄激素信号传导也会导致胸腺活性增加，包括 分子CCL 25，其反过来增强胸腺细胞前体向胸腺的迁移。 发现在这种情况下，CCL 25对于上调胸腺功能是必需的。两 这些增加胸腺功能并进而增强T细胞免疫的方法， 在癌症治疗环境中的重建可以应用于临床试验。

As noted in the goals and objectives stated for this project, it aims to create new models that test distinct hypotheses and provide new understandings for development of novel strategies in the treatment of lymphoma, myeloma, leukemia, breast cancer and renal cancer by hematopoietic stem cell transplantation. Hematopoietic stem cell transplant treatment of these diseases generally results in lymphopenia and immune compromise. The observation that in humans there is the ability to upregulate thymus function in the setting of cancer therapy-associated lymphopenia has been translated to murine models. We have initiated four parallel efforts to identify points of control in thymus function. In experiments utilizing IGF-1, which was found to upregulate thymus activity, we observed that while thymocyte precursor pool size and molecules involved in migration are affected, the critical control point was at the level of expanding maturational niches for incoming thymocytes. Cessation of androgen signaling, which also results in increased thymus activity, involved upregualtion of the molecule CCL25 which in turn enhanced immigation of thymocyte precusors into the thymus. CCL25 was found to be necessary for upregulation of thymus function in this setting. Both of these approaches for increasing thymus function and in turn enhancing T cell immune reconstitution in the setting of cancer therapy can be applied to clinical trials.