title: Decline of influenza-specific CD8+ T cell repertoire in healthy geriatric donors.
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 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Johns Hopkins University, 733 N Broadway BRB 632, Baltimore, MD, 21205, USA. jschnec1@jhmi.edu.
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Lee
authors.forename: Mathias
authors.initials: M
authors.lastname: Oelke
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Ramachandra
authors.forename: David H
authors.initials: DH
authors.lastname: Canaday
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Schneck