Czesnikiewicz-Guzik Marta, Lee Won-Woo, Cui Dapeng, Hiruma Yuko, Lamar David L, Yang Zhi-Zhang, Ouslander Joseph G, Weyand Cornelia M, Goronzy Jörg J
Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University School of Medicine, Atlanta, GA30322, USA.
Clin Immunol. 2008 Apr;127(1):107-18. doi: 10.1016/j.clim.2007.12.002. Epub 2008 Jan 28.
With increasing age, the competence of the immune system to fight infections and tumors declines. Age-dependent changes have been mostly described for human CD8 T cells, raising the question of whether the response patterns for CD4 T cells are different. Gene expression arrays of memory CD4 T cells yielded a similar age-induced fingerprint as has been described for CD8 T cells. In cross-sectional studies, the phenotypic changes were not qualitatively different for CD4 and CD8 T cells, but occurred much more frequently in CD8 T cells. Homeostatic stability partially explained this lesser age sensitivity of CD4 T cells. With aging, naïve and central memory CD8 T cells were lost at the expense of phenotypically distinct CD8 effector T cells, while effector CD4 T cells did not accumulate. However, phenotypic shifts on central memory T cells were also more pronounced in CD8 T cells. This distinct stability in cell surface marker expression can be reproduced in vitro. The data show that CD8 T cells are age sensitive by at least two partially independent mechanisms: fragile homeostatic control and gene expression instability in a large set of regulatory cell surface molecules.
随着年龄的增长，免疫系统对抗感染和肿瘤的能力会下降。年龄依赖性变化大多在人类CD8 T细胞中有所描述，这就引发了CD4 T细胞的反应模式是否不同的问题。记忆性CD4 T细胞的基因表达阵列产生了与CD8 T细胞类似的年龄诱导特征。在横断面研究中，CD4和CD8 T细胞的表型变化在性质上并无差异，但在CD8 T细胞中发生得更为频繁。稳态稳定性部分解释了CD4 T细胞对年龄的敏感性较低。随着年龄增长，初始和中枢记忆性CD8 T细胞减少，以表型不同的CD8效应T细胞为代价，而效应CD4 T细胞并未积累。然而，中枢记忆T细胞的表型转变在CD8 T细胞中也更为明显。这种细胞表面标志物表达的独特稳定性可以在体外重现。数据表明，CD8 T细胞至少通过两种部分独立的机制对年龄敏感：脆弱的稳态控制和大量调节性细胞表面分子中的基因表达不稳定性。
