Effros R B
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095-1732, USA.
Vaccine. 2000 Feb 25;18(16):1661-5. doi: 10.1016/s0264-410x(99)00503-4.
Aging is associated with the progressive increase of T cells that lack expression of the CD28 costimulatory molecule. Because CD28/B7 signal transduction is required for proliferation, T cells lacking CD28 gene expression are incapable of clonal expansion. To determine whether CD28- T cells are a separate lineage or, alternatively, are the progeny of formerly CD28+ T cells, we performed cell culture longitudinal analysis on the same population of T cells over time. Repeated antigen-induced T cell division ultimately leads to irreversible cell cycle arrest, shortened telomeres, loss of telomerase inducibility, and total absence of expression of CD28. This in vitro model has elucidated a novel facet of T cell biology that may explain the increased incidence of infection and cancer in the elderly.
衰老与缺乏CD28共刺激分子表达的T细胞数量逐渐增加有关。由于增殖需要CD28/B7信号转导，缺乏CD28基因表达的T细胞无法进行克隆扩增。为了确定CD28阴性T细胞是一个独立的谱系，还是以前CD28阳性T细胞的后代，我们对同一群T细胞进行了长期的细胞培养分析。反复的抗原诱导T细胞分裂最终导致不可逆的细胞周期停滞、端粒缩短、端粒酶诱导性丧失以及CD28表达完全缺失。这个体外模型阐明了T细胞生物学的一个新方面，这可能解释了老年人感染和癌症发病率增加的原因。
