Barone K S, O'Brien P C, Stevenson J R
Department of Microbiology, Miami University, Oxford, Ohio 45056.
Cell Immunol. 1993 Apr 15;148(1):226-33. doi: 10.1006/cimm.1993.1105.
The purpose of this project was to characterize changes in murine T lymphocyte subpopulations during thymic atrophy induced by protein malnutrition and to determine the role of elevated serum corticosterone in this process. A suitable animal model was generated by placing mice on protein-sufficient (PS) and protein-deficient (PD) diets for 6 weeks. Body weight was monitored to determine the establishment and maintenance of malnutrition. Results obtained using PD mice indicated a direct correlation between serum corticosterone levels and thymic atrophy. Furthermore, results of the experiments using mice implanted with corticosterone-impregnated pellets indicated that corticosterone alone, at the levels observed in PD mice, induced thymic atrophy in normal mice. These results demonstrate that the thymic atrophy induced by protein malnutrition is primarily due to elevated serum corticosterone. As indicated by flow cytometric analysis, the number of cells in all thymocyte subpopulations decreased as protein malnutrition continued, possibly reflecting depletion of immature CD4-/CD8- and CD4+/CD8+ cells, ultimately resulting in loss of mature CD4+ and CD8+ cells. TCR expression by PD thymocytes, especially those with high levels of CD3, increased during the dietary period. Mice implanted with corticosterone pellets experienced severe losses of CD4+/CD8+ cells, resulting in thymocyte subpopulation and CD3 profiles more similar to those of hydrocortisone-injected mice than those of PD mice. Therefore, whereas thymic atrophy in protein-malnourished mice seems to be caused by elevated serum corticosterone, it appears that additional factors further modulate thymocyte proliferation, differentiation, and/or death in this system.
本项目的目的是描述蛋白质营养不良诱导的胸腺萎缩过程中小鼠T淋巴细胞亚群的变化，并确定血清皮质酮升高在此过程中的作用。通过将小鼠置于蛋白质充足（PS）和蛋白质缺乏（PD）饮食6周来建立合适的动物模型。监测体重以确定营养不良的建立和维持情况。使用PD小鼠获得的结果表明血清皮质酮水平与胸腺萎缩之间存在直接相关性。此外，使用植入含皮质酮微丸的小鼠进行的实验结果表明，仅皮质酮在PD小鼠中观察到的水平就可诱导正常小鼠发生胸腺萎缩。这些结果表明，蛋白质营养不良诱导的胸腺萎缩主要是由于血清皮质酮升高所致。流式细胞术分析表明，随着蛋白质营养不良的持续，所有胸腺细胞亚群中的细胞数量均减少，这可能反映了未成熟CD4-/CD8-和CD4+/CD8+细胞的耗竭，最终导致成熟CD4+和CD8+细胞的丢失。在饮食期间，PD胸腺细胞尤其是CD3水平高的细胞的TCR表达增加。植入皮质酮微丸的小鼠经历了CD4+/CD8+细胞的严重丢失，导致胸腺细胞亚群和CD3谱更类似于注射氢化可的松的小鼠而非PD小鼠。因此，虽然蛋白质营养不良小鼠的胸腺萎缩似乎是由血清皮质酮升高引起的，但似乎还有其他因素进一步调节该系统中胸腺细胞的增殖、分化和/或死亡。
