Tesar Bethany M, Walker Wendy E, Unternaehrer Julia, Joshi Nikhil S, Chandele Anmol, Haynes Laura, Kaech Susan, Goldstein Daniel R
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8018, USA.
Aging Cell. 2006 Dec;5(6):473-86. doi: 10.1111/j.1474-9726.2006.00245.x.
The immune response is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this interaction is unclear. Addressing this fundamental question will be critical for the development of effective vaccines for the rapidly rising older subpopulation that manifests increased prevalence of malignancies and infections. Therefore, we undertook the current study to investigate whether aging impairs toll-like receptor (TLR) function in myeloid dendritic cells and whether this leads to reduced T-cell priming. Our results demonstrate that innate TLR immune priming function of myeloid bone marrow derived and splenic dendritic cells (DC) is preserved with aging using both allogeneic and infectious murine experimental systems. In contrast, aging impairs in vitro and in vivo intrinsic T-cell function. Therefore, our results demonstrate that myeloid DCs manifest preserved TLR-mediated immune responses with aging. However, aging critically impairs intrinsic adaptive T-cell function.
免疫反应是先天免疫和适应性免疫相互作用的结果,但衰老对这种相互作用的影响尚不清楚。解决这个基本问题对于为迅速增加的老年亚人群开发有效的疫苗至关重要,这些老年人中恶性肿瘤和感染的患病率有所增加。因此,我们进行了当前的研究,以调查衰老是否会损害髓样树突状细胞中的Toll样受体(TLR)功能,以及这是否会导致T细胞启动减少。我们的结果表明,使用同种异体和感染性小鼠实验系统,随着衰老,骨髓来源的髓样树突状细胞和脾脏树突状细胞(DC)的先天TLR免疫启动功能得以保留。相比之下,衰老会损害体外和体内的固有T细胞功能。因此,我们的结果表明,随着衰老,髓样DC表现出保留的TLR介导的免疫反应。然而,衰老严重损害了固有的适应性T细胞功能。