Decline of influenza-specific CD8+ T cell repertoire in healthy geriatric donors

Decline of influenza-specific CD8+ T cell repertoire in healthy geriatric donors

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Abstract Background 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.Results 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 Handbags and Wallets 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 Carb Caps 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).Conclusion 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.