Frontiers in Immunology (Sep 2018)

Short Lifespans of Memory T-cells in Bone Marrow, Blood, and Lymph Nodes Suggest That T-cell Memory Is Maintained by Continuous Self-Renewal of Recirculating Cells

  • Mariona Baliu-Piqué,
  • Myrddin W. Verheij,
  • Julia Drylewicz,
  • Lars Ravesloot,
  • Lars Ravesloot,
  • Rob J. de Boer,
  • Ad Koets,
  • Ad Koets,
  • Kiki Tesselaar,
  • José A. M. Borghans

DOI
https://doi.org/10.3389/fimmu.2018.02054
Journal volume & issue
Vol. 9

Abstract

Read online

Memory T-cells are essential to maintain long-term immunological memory. It is widely thought that the bone marrow (BM) plays an important role in the long-term maintenance of memory T-cells. There is controversy however on the longevity and recirculating kinetics of BM memory T-cells. While some have proposed that the BM is a reservoir for long-lived, non-circulating memory T-cells, it has also been suggested to be the preferential site for memory T-cell self-renewal. In this study, we used in vivo deuterium labeling in goats to simultaneously quantify the average turnover rates—and thereby expected lifespans—of memory T-cells from BM, blood and lymph nodes (LN). While the fraction of Ki-67 positive cells, a snapshot marker for recent cell division, was higher in memory T-cells from blood compared to BM and LN, in vivo deuterium labeling revealed no substantial differences in the expected lifespans of memory T-cells between these compartments. Our results support the view that the majority of memory T-cells in the BM are self-renewing as fast as those in the periphery, and are continuously recirculating between the blood, BM, and LN.

Keywords