Aspinall R, Andrew D
Department of Immunology, ICSM at Chelsea and Westminster Hospital, 369 Fulham Road, London, UK.
Vaccine. 2000 Feb 25;18(16):1629-37. doi: 10.1016/s0264-410x(99)00498-3.
Age related deterioration in the function of the immune system has been recognised in many species. The clinical presentations of such immune dysfunction are an age-related increased susceptibility to certain infections, and an increased incidence of autoimmune disease and certain cancers. Laboratory investigations reveal a reduced ability of the cells from older individuals, compared with younger individuals, to perform in functional in vitro assays. These manifestations are thought to be causally linked to an age associated involution of the thymus, which precedes the onset of immune dysfunction. Hypotheses to account for the age-related changes in the thymus include: (i) an age related decline in the supply of T cell progenitors from the bone marrow (ii) an intrinsic defect in the marrow progenitors, or (iii) problems with rearrangement of the TCR beta chain because of a defect in the environment provided by the thymus. We have analysed these possible options in normal mice and also in mice carrying a transgenic T cell receptor. The results from these studies reveal no age related decline either in the number of function of T cell progenitors in the thymus, but changes in the thymic environment in terms of the cytokines produced. We have shown that specific cytokine replacement therapy leads to an increase in thymopoiesis in old animals.
许多物种都已认识到与年龄相关的免疫系统功能衰退。这种免疫功能障碍的临床表现包括与年龄相关的对某些感染易感性增加、自身免疫性疾病和某些癌症的发病率上升。实验室研究表明，与年轻个体相比，老年个体的细胞在体外功能试验中的表现能力下降。这些表现被认为与胸腺的年龄相关退化存在因果联系，而胸腺退化先于免疫功能障碍的发生。解释胸腺与年龄相关变化的假设有：（i）骨髓中T细胞祖细胞供应的年龄相关下降；（ii）骨髓祖细胞的内在缺陷；或（iii）由于胸腺提供的环境缺陷导致TCRβ链重排问题。我们在正常小鼠以及携带转基因T细胞受体的小鼠中分析了这些可能的情况。这些研究结果显示，胸腺中T细胞祖细胞的数量或功能均未出现与年龄相关的下降，但胸腺环境在产生的细胞因子方面发生了变化。我们已经表明，特定的细胞因子替代疗法可导致老年动物胸腺生成增加。
