Wallace Diana L, Zhang Yan, Ghattas Hala, Worth Andrew, Irvine Andrew, Bennett Andrea R, Griffin George E, Beverley Peter C L, Tough David F, Macallan Derek C
Edward Jenner Institute for Vaccine Research, Compton, United Kingdom.
J Immunol. 2004 Aug 1;173(3):1787-94. doi: 10.4049/jimmunol.173.3.1787.
The age-associated decline in immunocompetence is paralleled by changes in the proportions of PBL subpopulations. In turn, the size and composition of the peripheral lymphocyte pool is determined by input from the thymus and bone marrow and by the balance of proliferation and death in each lymphocyte subpopulation. We compared the kinetics of lymphocyte subtypes in young (seven of eight CMV seronegative) and healthy elderly human subjects (six of seven CMV seropositive), using deuterated glucose DNA labeling in vivo to measure rates of T cell proliferation and disappearance. For CD45RO(+) cells of both CD4(+) and CD8(+) subtypes and for CD4(+)CD45RA(+) cells the kinetics of proliferation and disappearance were remarkably similar between elderly and young subjects. In the young, the kinetics of CD8(+)CD45RA(+) cells with a naive phenotype resembled those of CD4(+)CD45RA(+) cells. However, CD8(+)CD45RA(+) T cells from the elderly exhibited a predominantly primed phenotype, and for this subset, although the proliferation rate was similar to that of other CD45RA(+) cells, the disappearance rate of labeled cells was greatly decreased compared with that of all other T cell subsets. Our data provide a direct demonstration that there are no substantial changes in in vivo kinetics for most T cell populations in healthy elderly compared with young subjects. However, primed CD8(+)CD45RA(+) cells show unusual kinetic properties, indicating the persistence of these cells in the blood and dissociation of proliferation from disappearance.
免疫能力随年龄增长而下降,同时外周血淋巴细胞(PBL)亚群的比例也发生变化。反过来,外周淋巴细胞库的大小和组成由胸腺和骨髓的输入以及每个淋巴细胞亚群中增殖与死亡的平衡所决定。我们比较了年轻(8名巨细胞病毒血清阴性者中的7名)和健康老年人类受试者(7名巨细胞病毒血清阳性者中的6名)淋巴细胞亚型的动力学,采用体内氘代葡萄糖DNA标记来测量T细胞增殖和消失的速率。对于CD4(+)和CD8(+)亚型的CD45RO(+)细胞以及CD4(+)CD45RA(+)细胞,老年和年轻受试者之间增殖和消失的动力学非常相似。在年轻人中,具有初始表型的CD8(+)CD45RA(+)细胞的动力学类似于CD4(+)CD45RA(+)细胞。然而,来自老年人的CD8(+)CD45RA(+) T细胞主要表现为致敏表型,对于该亚群,尽管增殖速率与其他CD45RA(+)细胞相似,但标记细胞的消失速率与所有其他T细胞亚群相比大大降低。我们的数据直接表明,与年轻受试者相比,健康老年人中大多数T细胞群体的体内动力学没有实质性变化。然而,致敏的CD8(+)CD45RA(+)细胞表现出不同寻常的动力学特性,表明这些细胞在血液中的持续存在以及增殖与消失的分离。