Janković Vladimir, Messaoudi Ilhem, Nikolich-Zugich Janko
Vaccine and Gene Therapy Institute and Division of Pathobiology, Oregon National Primate Research Center, Beaverton, OR, USA.
Blood. 2003 Nov 1;102(9):3244-51. doi: 10.1182/blood-2003-03-0927. Epub 2003 Jul 17.
A prominent theory of immune senescence holds that repeated antigenic stimulation and decreased production of naive cells combine to progressively exhaust the reserve of lymphocytes available to fight new pathogens, culminating in an accumulation of lymphocytes that achieved replicative senescence. A well-defined primate model of immune senescence in vivo would greatly facilitate testing of this theory. Here, we investigated phenotypic and functional T-cell aging in the rhesus macaques (RMs), currently the dominant primate model of AIDS. Our results show that sharp differences exist between the CD8 and CD4 T-cell subsets in (1) cell-cycle programs (as assessed by both in vitro proliferation and in vivo turnover measurement); (2) CD28 regulation on cell-cycle entry; and (3) accumulation of immediate effector cells among the CD28- cells, believed to be close to or at replicative senescence. These results further suggest poor reliability of CD28 as a marker for senescence. We suggest that some of the T-cell aging phenomenology in RMs can be ascribed to accentuation over time of the inherent differences in activation programs in CD8 and CD4 T cells.
一种著名的免疫衰老理论认为，反复的抗原刺激和幼稚细胞产生的减少共同作用，逐渐耗尽了可用于对抗新病原体的淋巴细胞储备，最终导致达到复制衰老的淋巴细胞积累。一个明确的体内免疫衰老灵长类动物模型将极大地促进对该理论的测试。在这里，我们研究了恒河猴（RMs）中T细胞的表型和功能衰老，恒河猴是目前主要的艾滋病灵长类动物模型。我们的结果表明，CD8和CD4 T细胞亚群在以下方面存在明显差异：（1）细胞周期程序（通过体外增殖和体内更新测量评估）；（2）CD28对细胞周期进入的调节；（3）在CD28-细胞中即时效应细胞的积累，这些细胞被认为接近或处于复制衰老状态。这些结果进一步表明CD28作为衰老标志物的可靠性较差。我们认为，恒河猴中一些T细胞衰老现象可归因于随着时间的推移，CD8和CD4 T细胞激活程序中固有差异的加剧。
