Scientific Reports (Jul 2017)

Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells

  • Martine J. Kallemeijn,
  • Anne Mieke H. Boots,
  • Michèle Y. van der Klift,
  • Elisabeth Brouwer,
  • Wayel H. Abdulahad,
  • Jan A. N. Verhaar,
  • Jacques J. M. van Dongen,
  • Anton W. Langerak

DOI
https://doi.org/10.1038/s41598-017-05849-1
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 14

Abstract

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Abstract 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.