Aging · Feb 12, 2020
Orai, STIM, and PMCA contribute to reduced calcium signal generation in CD8⁺ T cells of elderly mice
By Angenendt A, Steiner R, Knörck A et al.
Ca²⁺ is a crucial second messenger for proper T cell function. Considering the relevance of Ca²⁺ signals for T cell functionality it is surprising that no mechanistic insights into T cell Ca²⁺ signals from elderly individuals are reported. The main Ca²⁺ entry mechanism in T cells are STIM-activated Orai channels. Their role during lymphocyte aging is completely unknown. Here, we report not only reduced Ca²⁺ signals in untouched and stimulated, but also in central and effector memory CD8⁺ T cells from elderly (18-24 months) compared to adult (3-6 months) mice. Two mechanisms contribute to the overall reduction in Ca²⁺ signals of CD8⁺ T cells of elderly mice: 1) Reduced Ca²⁺ currents through Orai channels due to decreased expressions of STIMs and Orais. 2) A faster extrusion of Ca²⁺ owing to an increased expression of PMCA4. The reduced Ca²⁺ signals correlated with a resistance of the cytotoxic efficiency of CD8⁺ T cells to varying free [Ca²⁺]ext with age. In summary, reduced STIM/Orai expression and increased Ca²⁺ clearing rates following enhanced PMCA4 expression contribute to reduced Ca²⁺ signals in CD8⁺ T cells of elderly mice. These changes are apparently relevant to immune function as they reduce the Ca²⁺ dependency of CTL cytotoxicity.