Van Epps Puja, Banks Richard, Aung Htin, Betts Michael R, Canaday David H
Geriatric Research Center Clinical Core (GRECC), Louis Stokes Cleveland VA Medical Center, 10701 East Blvd, Cleveland, Ohio 44106, USA ; Division of Infectious Diseases, Case Western Reserve University School of Medicine, 10900 Euclid Ave, BRB 1022, Cleveland, Ohio, 44106-4684, USA.
Geriatric Research Center Clinical Core (GRECC), Louis Stokes Cleveland VA Medical Center, 10701 East Blvd, Cleveland, Ohio 44106, USA.
Immun Ageing. 2014 Oct 23;11:14. doi: 10.1186/1742-4933-11-14. eCollection 2014.
A reduced number of naïve T cells along with an accumulation of differentiated cell types in aging have been described but little is known about the polyfunctionality of the T cell responses. In this study we compared the individual and polyfunctional expression of IFN-γ, MIP-1α, TNF-α, perforin, and IL-2 by T cell subsets, including the newly described stem cell like memory T cells (TSCM), in response to stimulation with superantigen staphylococcal enterotoxin B (SEB) in older (median age 80, n = 23) versus younger (median age 27; n = 23) adults.
Older age was associated with a markedly lower frequency of CD8+ naïve T cells (11% vs. 47%; p < 0.0001) and an expansion in memory T cell subsets including central memory (p < 0.05), effector memory and effector T cells (p < 0.001 for both). There was also a decline in CD4+ naïve T cells in older subjects (33% vs. 45%; p = 0.02). There were no differences in frequencies or polyfunctional profiles of TSCM between groups. CD8+ naïve cells in the older group had increased expression of all functional parameters measured compared to the younger subjects and exhibited greater polyfunctionality (p = 0.04). CD4+ naïve T cells in the older group also showed greater polyfunctionality with a TNF-α and IL-2 predominance (p = 0.005). CD8+ effector memory and effector T cells exhibited increased polyfunctionality in the older group compared with younger (p = 0.01 and p = 0.003).
These data suggest that aging does not have a negative effect on polyfunctionality and therefore this is likely not a major contributor to the immunesenescence described with aging.
已有研究报道，衰老过程中初始T细胞数量减少，同时分化细胞类型积累，但对于T细胞反应的多功能性了解甚少。在本研究中，我们比较了老年（中位年龄80岁，n = 23）与年轻（中位年龄27岁；n = 23）成年人的T细胞亚群，包括新描述的干细胞样记忆T细胞（TSCM），在超抗原葡萄球菌肠毒素B（SEB）刺激下，IFN-γ、MIP-1α、TNF-α、穿孔素和IL-2的个体及多功能表达情况。
老年与CD8⁺初始T细胞频率显著降低相关（11%对47%；p < 0.0001），记忆T细胞亚群包括中枢记忆（p < 0.05）、效应记忆和效应T细胞（两者均p < 0.001）出现扩增。老年受试者中CD4⁺初始T细胞也有所下降（33%对45%；p = 0.02）。两组之间TSCM的频率或多功能谱无差异。与年轻受试者相比，老年组的CD8⁺初始细胞在所测所有功能参数上的表达均增加，且表现出更大的多功能性（p = 0.04）。老年组的CD4⁺初始T细胞也表现出更大的多功能性，以TNF-α和IL-2为主（p = 0.005）。与年轻组相比，老年组的CD8⁺效应记忆和效应T细胞表现出更高的多功能性（p = 0.01和p = 0.003）。
这些数据表明，衰老对多功能性没有负面影响，因此这可能不是衰老所致免疫衰老的主要因素。
