Functional Consequences of Increased Virus-specific CD8+ Effector Memory T cells in the Response to Influenza in Older Adults (130.4)

Abstract

Abstract Background: The decline in adaptive immune function with age is a major cause for increased risk of complicated influenza illness in older adults especially those with congestive heart failure (CHF). Changes in the CD8+ T cell response to the virus may explain the increased risk of influenza in the older population. Methods: The response to influenza in 12-hour peripheral blood mononuclear cell (PBMC) cultures from vaccinated healthy young (20-40 y.o.) and older adults (age =60 y.o.) with or without CHF was measured in different CD8+ T cell subsets. Results: In unstimulated PBMC, older compared to young adults showed a higher proportion of GrB+CD8+ T cells, and these T cells also expressed higher levels of CD107a in the CHF group. Healthy young and older adults showed a significant increase in the GrzB+CD8+ T cells expressing CD107a, consistent with a cytolytic effector function; older adults with CHF had no response. Preliminary results suggest that this poor response is associated with an increased proportion of terminally-differentiated, effector memory (CD8+CD45RA+) T cells. Conclusions: An accumulation of terminally differentiated CD8+CD45RA+ T cells have an effector phenotype but do not respond to influenza virus and may explain the increased risk of influenza in the older adults.