Abstract
The impact of ageing on the immune system results in defects in T cell responsiveness. The search for ageing hallmarks has been challenging due to the complex nature of immune responses in which the kinetics of T cell responsiveness have largely been neglected. We aimed to unravel hallmarks of ageing in the kinetics of the murine T cell response. To this end, we assessed ageing-related T-cell response kinetics by studying the effect of the duration and strength of in vitro stimulation on activation, proliferation, and cytokine secretion by T cells of young and aged mice. Collectively, our data show that stimulatory strength and time kinetics of cytokine secretion, activation markers, and proliferation of Th, Tc, and Treg cells are crucial in understanding the impact of ageing on T cells. Despite low proliferative capacity, T cell subsets of aged mice do respond to stimulation by upregulation of activation markers and secretion of cytokines. These findings therefore indicate that replicative senescence of aged T cells is not a measure of unresponsiveness per se, but rather stress that ageing influences the kinetics of proliferation, upregulation of activation markers and cytokine secretion each to a different extent.
Highlights
The immune system reflects consequences of ageing by many alterations in the T-cell population that compromise T-cell responsiveness at old age[1,2]
We investigated the impact of ageing on T-cell response kinetics by studying the effect of the duration and strength of in vitro stimulation on T-cell activation markers, proliferation, and cytokine secretion in young and aged mice
Our study shows that T-cell response kinetics are a valuable tool to better understand the impact of ageing on T cells
Summary
The immune system reflects consequences of ageing by many alterations in the T-cell population that compromise T-cell responsiveness at old age[1,2]. We assessed ageing-related T-cell response kinetics by studying the effect of the duration and strength of in vitro stimulation on activation, proliferation, and cytokine secretion by T cells of young and aged mice. Reduced proliferation is a major characteristic of T-cell senescence[6] As both proliferation and expression of activation and inhibition markers by T-cell subsets are highly dynamic during an immune response, elucidating the kinetics of these parameters may reveal ageing-related alterations of T-cell responsiveness. We aimed to reveal the impact of ageing on T-cell responsiveness by assessing the in vitro response kinetics of cytokine secretion, activation marker upregulation, and proliferation of T cells of young and aged mice in response to antigen-independent stimulation. Our findings stress the importance of addressing T-cell response kinetics and the strength of stimuli used to characterise the impact of ageing on the T cell compartment
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