Savino W
Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Eur J Clin Nutr. 2002 Aug;56 Suppl 3:S46-9. doi: 10.1038/sj.ejcn.1601485.
Malnutrition, secondary to deficiency in uptake of proteins, metal elements or vitamins, consistently results in changes in the thymus gland. The organ undergoes a severe atrophy due to apoptosis-induced thymocyte depletion, particularly affecting the immature CD4(+) CD8(+) cells, as well as a decrease in cell proliferation. Such a feature is apparently linked to a hormonal imbalance, involving decrease of leptin and consequent raise of glucocorticoid hormone levels in the serum. Interestingly, this picture can be reversed after appropriate diet rehabilitation. The thymic microenvironment is also affected in malnutrition: morphological changes in thymic epithelial cells were found, together with a decrease of thymic hormone production by these cells. Additionally, intrathymic contents of extracellular proteins, such as fibronectin, laminin and collagens, are increased in the thymuses from malnourished children. Conjointly, the bulk of data discussed herein clearly points to the notion that the thymus gland is a target in malnutrition. Nevertheless, further relevant information regarding the physiology of the thymus, including the cytokine/chemokine secretion as well as the positive and negative selection events driven by TCR/MHC-peptide interactions in malnutrition, remains to be defined. These are questions that need to be answered in order to have a better understanding of the immunodeficiency seen in malnourished individuals.
由于蛋白质、金属元素或维生素摄取不足导致的营养不良,始终会引起胸腺的变化。该器官会因凋亡诱导的胸腺细胞耗竭而发生严重萎缩,尤其会影响未成熟的CD4(+)CD8(+)细胞,同时细胞增殖也会减少。这种特征显然与激素失衡有关,包括瘦素减少以及血清中糖皮质激素水平随之升高。有趣的是,经过适当的饮食康复后,这种情况可以得到逆转。营养不良时胸腺微环境也会受到影响:发现胸腺上皮细胞有形态变化,同时这些细胞产生的胸腺激素减少。此外,营养不良儿童的胸腺中细胞外蛋白质(如纤连蛋白、层粘连蛋白和胶原蛋白)的胸腺内含量增加。总体而言,本文讨论的大量数据清楚地表明胸腺是营养不良的一个靶点。然而,关于胸腺生理学的进一步相关信息,包括营养不良时细胞因子/趋化因子的分泌以及由TCR/MHC-肽相互作用驱动的阳性和阴性选择事件,仍有待确定。为了更好地理解营养不良个体中出现的免疫缺陷,这些问题需要得到解答。