Aging Boosts Antiviral CD8+T Cell Memory Through Improved Engagement Of Diversified Recall Response Determinants

Abstract

The determinants of protective CD8+ memory T cell (CD8+TM) immunity remain incompletely defined and may in fact constitute an evolving agency as aging CD8+TM progressively acquire enhanced rather than impaired recall capacities. Here, we show that old as compared to young antiviral CD8+TM more effectively harness disparate molecular processes (cytokine signaling, trafficking, effector functions, and co-stimulation/inhibition) that in concert confer greater secondary reactivity. The relative reliance on these pathways is contingent on the nature of the secondary challenge (greater for chronic than acute viral infections) and over time, aging CD8+TM re-establish a dependence on the same accessory signals required for effective priming of naive CD8+T cells in the first place. Thus, our findings are consistent with the recently proposed \"rebound model\" that stipulates a gradual alignment of naive and CD8+TM properties, and identify a diversified collection of potential targets that may be exploited for the therapeutic modulation of CD8+TM immunity.