Lemster Bonnie H, Michel Joshua J, Montag David T, Paat John J, Studenski Stephanie A, Newman Anne B, Vallejo Abbe N
Department of Pediatrics, University of Pittsburgh, PA 15213, USA.
J Immunol. 2008 Feb 1;180(3):1979-90. doi: 10.4049/jimmunol.180.3.1979.
Degeneration of the thymus and severe contraction of the T cell repertoire with aging suggest that immune homeostasis in old age could be mediated by distinct effectors. Therefore, receptors expressed on T cells as they undergo senescence in vitro, as well as those displayed by circulating T cells during normal chronologic aging, were examined. Monitoring of T cells driven to senescence showed de novo induction of CD56, the prototypic receptor of NK cells. Analysis of fresh T cells in peripheral blood showed an age-dependent induction of CD56. These unusual T cells expressed high levels of Bcl2, p16, and p53, and had limited, or completely lost, ability to undergo cell division, properties consistent with senescence. CD56 cross-linking without TCR ligation on CD56(+) T cells resulted in extensive protein phosphorylation, NF-kappaB activation, and Bax down-regulation. CD56 cross-linking was also sufficient to drive production of various humoral factors. These data suggest that the immunologic environment in old age is functionally distinct, rather than being a dysfunctional version of that seen at a young age. CD56(+) T cells are unique effectors capable of mediating TCR-independent immune cascades that could be harnessed to enhance protective immunity in the elderly.
胸腺退化以及随着衰老T细胞库严重收缩，这表明老年期的免疫稳态可能由不同的效应器介导。因此，研究了T细胞在体外衰老过程中表达的受体，以及正常自然衰老过程中循环T细胞所展示的受体。对被诱导衰老的T细胞进行监测，发现NK细胞的原型受体CD56从头诱导表达。对外周血新鲜T细胞的分析显示，CD56的诱导呈现年龄依赖性。这些异常T细胞表达高水平的Bcl2、p16和p53，并且细胞分裂能力有限或完全丧失，这些特性与衰老一致。在CD56(+) T细胞上，不通过TCR连接而进行CD56交联会导致广泛的蛋白质磷酸化、NF-κB激活以及Bax下调。CD56交联也足以驱动各种体液因子的产生。这些数据表明，老年期的免疫环境在功能上是独特的，而非年轻时那种功能失调的版本。CD56(+) T细胞是独特的效应器，能够介导不依赖TCR的免疫级联反应，可利用这一点来增强老年人的保护性免疫。
