Daan Pieren

30 Chapter 2 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.