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

Abstract While the goal of influenza vaccination is to develop antibodies to protect against a primary infection, clearance of the infection is primarily mediated through CD8+ T cells. The study of the CD8+ T cell response to influenza epitopes is crucial in understanding the disease and associated morbidity and mortality. The age-associated decline of the immune system is believed to be responsible for the increased risk of influenza infection in the geriatric population. Since the CTL response is important for the clearance of influenza infection, we compared the CTL response to immunodominant and subdominant influenza epitopes in HLA-A2+ control adult donors, aged 21-42, to the response in healthy geriatric donors, aged 65 and older. This was done using an artificial Antigen Presenting Cell (aAPC) based stimulation assay which revealed responses that could not be detected by ELISpot. Control donors showed a broad, multi-specific response to the subdominant epitopes, and each donor’s subdominant influenza-specific response was unique. When comparing the control donors’ CTL response to the geriatric donors’, the immunodominant M1 responses were preserved, however, the geriatric donors lacked the broad multi-specific response to influenza-specific subdominant epitopes seen in the control donors. These data indicate 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.