Aw D, Silva A B, Palmer D B
Infection & Immunity and Genes & Development Group, Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
J Comp Pathol. 2010 Jan;142 Suppl 1:S45-59. doi: 10.1016/j.jcpa.2009.10.004. Epub 2009 Dec 8.
The immune system declines with age leading to a progressive deterioration in the ability to respond to infection and vaccination. Age-associated thymic involution is one of the most recognized changes in the ageing immune system and is believed to be a major contributor towards immunosenescence; however, the precise mechanisms involved in age-associated thymic involution remain unclear. In order to gain further insight into the effect of ageing on T-cell development, steady-state thymopoiesis was studied in mice ranging from 1 to 18 months of age. There was a decrease in thymic cellularity with age, but the most dramatic loss occurred early in life. Although there were no alterations in the proportion of the major thymocyte subsets, there was a significant decline in the expression of other key molecules including CD3 and CD24. There was a decline in the ability of thymocytes from older mice to respond to mitogens, which was demonstrated by a failure to up-regulate expression of the activation marker CD69 and to enter the G(2)--M phase of the cell cycle. This was concurrent with an increased resistance to apoptosis in thymocytes from aged animals. Together, these results suggest that T cells may be flawed even before exiting to the periphery and that this could contribute to the age-associated decline in immune function.
免疫系统会随着年龄的增长而衰退，导致机体对感染和疫苗接种的反应能力逐渐下降。与年龄相关的胸腺退化是衰老免疫系统中最广为人知的变化之一，被认为是免疫衰老的主要促成因素；然而，与年龄相关的胸腺退化所涉及的精确机制仍不清楚。为了进一步深入了解衰老对T细胞发育的影响，研究人员对1至18月龄小鼠的稳态胸腺生成进行了研究。胸腺细胞数量随年龄增长而减少，但最显著的减少发生在生命早期。虽然主要胸腺细胞亚群的比例没有变化，但包括CD3和CD24在内的其他关键分子的表达显著下降。老年小鼠胸腺细胞对有丝分裂原的反应能力下降，这表现为无法上调激活标记CD69的表达以及进入细胞周期的G(2)-M期。这与老年动物胸腺细胞对凋亡的抵抗力增加同时发生。这些结果共同表明，T细胞甚至在进入外周之前可能就存在缺陷，这可能导致与年龄相关的免疫功能下降。
