Department of Pathology, Johns Hopkins University, 733 N Broadway BRB 632, Baltimore, MD, 21205, USA.
Immun Ageing. 2011 Aug 16;8:6. doi: 10.1186/1742-4933-8-6.
While influenza vaccination results in protective antibodies against primary infections, clearance of infection is primarily mediated through CD8+ T cells. Studying the CD8+ T cell response to influenza epitopes is crucial in understanding the disease associated morbidity and mortality especially in at risk populations such as the elderly. We compared the CD8+ T cell response to immunodominant and subdominant influenza epitopes in HLA-A2+ control, adult donors, aged 21-42, and in geriatric donors, aged 65 and older.
We used a novel artificial Antigen Presenting Cell (aAPC) based stimulation assay to reveal responses that could not be detected by enzyme-linked immunosorbent spot (ELISpot). 14 younger control donors and 12 geriatric donors were enrolled in this study. The mean number of influenza-specific subdominant epitopes per control donor detected by ELISpot was only 1.4 while the mean detected by aAPC assay was 3.3 (p = 0.0096). Using the aAPC assay, 92% of the control donors responded to at least one subdominant epitopes, while 71% of control donors responded to more than one subdominant influenza-specific response. 66% of geriatric donors lacked a subdominant influenza-specific response and 33% of geriatric donors responded to only 1 subdominant epitope. The difference in subdominant response between age groups is statistically significant (p = 0.0003).
Geriatric donors lacked the broad, multi-specific response to subdominant epitopes seen in the control donors. Thus, we conclude that aging leads to a decrease in the subdominant influenza-specific CTL responses which may contribute to the increased morbidity and mortality in older individuals.
流感疫苗接种可产生针对初次感染的保护性抗体，但清除感染主要通过 CD8+T 细胞介导。研究针对流感表位的 CD8+T 细胞反应对于了解相关发病率和死亡率至关重要，尤其是在高危人群如老年人中。我们比较了 HLA-A2+对照、年龄在 21-42 岁的成年供体和年龄在 65 岁及以上的老年供体中免疫优势和亚优势流感表位的 CD8+T 细胞反应。
我们使用新型人工抗原呈递细胞（aAPC）刺激测定法来揭示无法通过酶联免疫斑点（ELISpot）检测到的反应。本研究纳入了 14 名年轻对照供体和 12 名老年供体。ELISpot 检测到的平均每位对照供体的流感亚优势表位数量仅为 1.4 个，而 aAPC 测定法检测到的平均数量为 3.3 个（p=0.0096）。使用 aAPC 测定法，92%的对照供体至少对一个亚优势表位有反应，而 71%的对照供体对多个亚优势流感特异性反应有反应。66%的老年供体缺乏亚优势流感特异性反应，而 33%的老年供体仅对 1 个亚优势表位有反应。年龄组之间的亚优势反应差异具有统计学意义（p=0.0003）。
老年供体缺乏对照供体中所见的针对亚优势表位的广泛、多特异性反应。因此，我们得出结论，衰老导致亚优势流感特异性 CTL 反应减少，这可能导致老年人发病率和死亡率增加。
