Early priming minimizes the age-related immune compromise of CD8+ T cell diversity and function

The elderly are particularly susceptible to influenza a virus infections,with increased occurrence,disease severity and reduced vaccine efficacy attributed to declining immunity. experimentally,the age-dependent decline in influenza-specific cd8+ t cell responsiveness reflects both functional compromise and the emergence of 'repertoire holes' arising from the loss of low frequency clonotypes. in this study,we asked whether early priming limits the time-related attrition of immune competence. though primary responses in aged mice were compromised,animals vaccinated at 6 weeks then challenged >20 months later had t-cell responses that were normal in magnitude. both functional quality and the persistence of 'preferred' tcr clonotypes that expand in a characteristic immunodominance hierarchy were maintained following early priming. similar to the early priming,vaccination at 22 months followed by challenge retained a response magnitude equivalent to young mice. however,late priming resulted in reduced tcrβ diversity in comparison with vaccination earlier in life. thus,early priming was critical to maintaining individual and population-wide tcrβ diversity. in summary,early exposure leads to the long-term maintenance of memory t cells and thus preserves optimal,influenza-specific cd8+ t-cell responsiveness and protects against the age-related attrition of naïve t-cell precursors. our study supports development of vaccines that prime cd8+ t-cells early in life to elicit the broadest possible spectrum of cd8+ t-cell memory and preserve the magnitude,functionality and tcr usage of responding populations. in addition,our study provides the most comprehensive analysis of the aged (primary,secondary primed-early and secondary primed-late) tcr repertoires published to date. © 2012 valkenburg et al.