Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells
Ageing is a broad cellular process, largely affecting the immune system, especially T-lymphocytes. Additionally to immunosenescence alone, cytomegalovirus (CMV) infection is thought to have major impacts on T-cell subset composition and exhaustion. These impacts have been studied extensively in TCRαβ+ T-cells, with reduction in naive, increase in effector (memory) subsets and shifts in CD4/CD8-ratios, in conjunction with morbidity and mortality in elderly. Effects of both ageing and CMV on the TCRγδ+ T-cell compartment remain largely elusive. In the current study we investigated Vγ- and Vδ-usage, maturation, differentiation and exhaustion marker profiles of both CD4 and CD8 double-negative (DN) and CD8+TCRγδ+ T-cells in 157 individuals, age range 20–95. We observed a progressive decrease in absolute numbers of total TCRγδ+ T-cells in blood, affecting the predominant Vγ9/Vδ2 population. Aged TCRγδ+ T-cells appeared to shift from naive to more (late-stage) effector phenotypes, which appeared more prominent in case of persistent CMV infections. In addition, we found effects of both ageing and CMV on the absolute counts of exhausted TCRγδ+ T-cells. Collectively, our data show a clear impact of ageing and CMV persistence on DN and CD8+TCRγδ+ T-cells, similar to what has been reported in CD8+TCRαβ+ T-cells, indicating that they undergo similar ageing processes.
|Persistent URL||dx.doi.org/10.1038/s41598-017-05849-1, hdl.handle.net/1765/101184|
Kallemeijn, M.J, Boots, A.M.H, van der Klift, M.Y, Brouwer, E, Abdulahad, W.H. (Wayel H.), Verhaar, J.A.N, … Langerak, A.W. (2017). Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells. Scientific Reports, 7(1). doi:10.1038/s41598-017-05849-1