Dataset Information

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.

ABSTRACT: 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.

SUBMITTER: Baliu-Pique M

PROVIDER: S-EPMC6141715 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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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.

Baliu-Piqué Mariona M Verheij Myrddin W MW Drylewicz Julia J Ravesloot Lars L de Boer Rob J RJ Koets Ad A Tesselaar Kiki K Borghans José A M JAM

Frontiers in immunology 20180911

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 <i> ...[more]

PMID: 30254637

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Project description:Naive T lymphocytes exhibit extensive antigen-independent recirculation between blood and lymph nodes, where they may encounter dendritic cells carrying cognate antigen. We examine how long different T cells may spend in an individual lymph node by examining data from long term cannulation of blood and efferent lymphatics of a single lymph node in the sheep. We determine empirically the distribution of transit times of migrating T cells by applying the Least Absolute Shrinkage & Selection Operator (LASSO) or regularised S-LASSO to fit experimental data describing the proportion of labelled infused cells in blood and efferent lymphatics over time. The optimal inferred solution reveals a distribution with high variance and strong skew. The mode transit time is typically between 10 and 20 hours, but a significant number of cells spend more than 70 hours before exiting. We complement the empirical machine learning based approach by modelling lymphocyte passage through the lymph node insilico. On the basis of previous two photon analysis of lymphocyte movement, we optimised distributions which describe the transit times (first passage times) of discrete one dimensional and continuous (Brownian) three dimensional random walks with drift. The optimal fit is obtained when drift is small, i.e. the ratio of probabilities of migrating forward and backward within the node is close to one. These distributions are qualitatively similar to the inferred empirical distribution, with high variance and strong skew. In contrast, an optimised normal distribution of transit times (symmetrical around mean) fitted the data poorly. The results demonstrate that the rapid recirculation of lymphocytes observed at a macro level is compatible with predominantly randomised movement within lymph nodes, and significant probabilities of long transit times. We discuss how this pattern of migration may contribute to facilitating interactions between low frequency T cells and antigen presenting cells carrying cognate antigen.

Dataset Information

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.

Publications

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.

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