Journal
FRONTIERS IN IMMUNOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.02054
Keywords
bone marrow; memory T-cells; lymphocyte turnover; lifespan; stable isotope labeling; deuterium; mathematical modeling
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Funding
- European Union Seventh Framework Programme (FP7/2007-2013) through Marie-Curie Action Quantitative T cell Immunology Initial Training Network [FP7-PEOPLE-2012-ITN 317040-QuanTI]
- Dutch Ministry of Agriculture, Nature and Food Quality [WOT-01-002-002.02]
- Dutch Public-Private Partnership Small Ruminants program
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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.
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