%0 Journal Article
%T Decline of influenza-specific CD8+ T cell repertoire in healthy geriatric donors
%A Jessica B Lee
%A Mathias Oelke
%A Lakshmi Ramachandra
%A David H Canaday
%A Jonathan P Schneck
%J Immunity & Ageing
%D 2011
%I BioMed Central
%R 10.1186/1742-4933-8-6
%X 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.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 [3-7]. While antibodies protect against development of primary influenza infection, clearance of the infection is chiefly mediated through CD8+ T cells [8,9]. It has been shown that CD8+ T cells are protective against influenza infection and are critical for the clearance of influenza infection in animal models [10-15]. Thus, 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.In influenza, the HLA-A2 restricted response to the matrix protein peptide, M158-66, is considered to be immunodominant [
%U http://www.immunityageing.com/content/8/1/6