Abstract
BackgroundWhile 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.ResultsWe 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).ConclusionGeriatric 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.
Highlights
While influenza vaccination results in protective antibodies against primary infections, clearance of infection is primarily mediated through CD8+ T cells
Using the artificial Antigen Presenting Cell (aAPC) assay to stimulate influenza-specific CD8+ T cells ex vivo from younger control donors, aged 21-42, and geriatric donors, over the age of 65, we found responses against the immunodominant influenza M158-66 peptide in both control and geriatric groups
The mean number of subdominant epitopes per donor detected by enzyme-linked immunosorbent spot (ELISpot) was only 1.4 while the mean detected by aAPC assay was statistically higher at 3.3, p = 0.0096 (Figure 3C)
Summary
While influenza vaccination results in protective antibodies against primary infections, clearance of infection is primarily mediated through CD8+ T cells. In the United States, it is estimated that more than 30,000 people die each year as a result of influenza infection with over 90% of deaths in individuals over age 65 [1,2]. This is due, in part, to the diminished immune response in the elderly [3,4,5,6,7]. It is necessary to study host CD8+ T cell response to influenza epitopes for a better understanding of susceptibility and changes that occur with aging.
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