THE STEM CELL - THYMUS AXIS

这项拟议的研究的目的是更全面地了解 胸腺在原胸腺细胞分化中的作用 胎鼠、幼年鼠和老年鼠的T淋巴细胞。在体外和体内 将采用活体技术。胎儿卵黄囊中的干细胞 肝脏、青年骨髓和老年骨髓将通过以下方法分离 通过对介质的化学吸引来利用它们的迁移倾向 由新生儿胸腺或胸腺上皮(T-E)细胞调节。单元格来自 由培养的干细胞在刺激因子刺激下形成的克隆 胸腺上皮细胞，将被检测T淋巴细胞的存在 霍奇金淋巴瘤的抗原标志物、T淋巴细胞功能和形态标志 差异化。研究免疫衰老在多大程度上 胸腺随着年龄的增长而退化，老年小鼠将被注射 将T-E细胞接种于葡聚糖珠上皮下培养。它的效果是 T-E细胞产生的因子对T淋巴细胞恢复的影响 功能将通过检测脾细胞产生IL-2来衡量， 对刀豆蛋白A的反应和细胞毒性。将对骨髓细胞进行测试 它们对胸腺上清液的体外和体内化学吸引作用 迁移到受辐射宿主的胸腺。注射用中的淋巴细胞 现场将检查胸腺细胞标志物。无菌小鼠将会是 对T淋巴细胞的产生进行类似的处理和测试。通过这件事 研究，T-E细胞产生的因子产生的能力 T淋巴细胞功能将被建立。这项基础研究将是 有助于为由以下原因引起的疾病过程开发合理的治疗方法 免疫系统的畸形、故障或老化。

The aim of this proposed research is to more completely understand the role played by the thymus in the differentiation of prothymocytes to T-lymphocytes in fetal, young adult and aged mice. Both in vitro and in vivo techniques will be employed. Stem cells from the yolk sac, fetal liver, young adult bone marrow and aged bone marrow will be isolated by utilizing their propensity to migrate by chemoattraction to media conditioned by newborn thymus or thymic epithelial (T-E) cells. Cells from colonies formed by cultured stem cells stimulated by factors produced by thymic epithelial cells, will be tested for the presence of T-lymphocyte antigenic markers, T-lymphocyte function, and morphologic signs of differentiation. To study the extent to which immunosenescence is a result of the thymus degenerating with age, aged mice will be injected subcutaneously with T-E cells cultured on dextran beads. The effect which factors produced by the T-E cells have on the restoration of T-lymphocyte function will be measured by examining spleen cells for IL-2 production, response to Con A and for cytotoxicity. Bone marrow cells will be tested for their in vitro chemoattraction to thymic supernatant and in vivo migration to the thymus of irradiated hosts. Lymphocytes in the injection site will be examined for thymocyte markers. Athymic mice will be similarly treated and tested for generation of T-lymphocytes. Through this study, the capacity of factors produced by T-E cells to generate T-lymphocyte function will be established. This basic research will be useful in developing rational therapy for disease processes resulting from malformation, malfunction, or aging of the immune system.