The natural history of naive T cells from birth to maturity

Seddon, Benedict; Yates, Andrew J.

doi:10.1111/imr.12694

Cited by 26 publications

(16 citation statements)

References 129 publications

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“…Another aspect of the compartments we sorted using the markers is that these are some of the T cells previously addressed as naïve, while in fact this is not a homogeneous pool of cells awaiting activation. The compartment previously addressed as naïve T cells is actually a complex mixture of cells at different developmental stages and of diverse ages [39]. Further, there are inflows of new cells from the naive pool that strongly impact memory cell [40].…”

Section: Discussionmentioning

confidence: 99%

Breast cancer is marked by specific, Public T-cell receptor CDR3 regions shared by mice and humans

et al. 2021

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The partial success of tumor immunotherapy induced by checkpoint blockade, which is not antigen-specific, suggests that the immune system of some patients contain antigen receptors able to specifically identify tumor cells. Here we focused on T-cell receptor (TCR) repertoires associated with spontaneous breast cancer. We studied the alpha and beta chain CDR3 domains of TCR repertoires of CD4 T cells using deep sequencing of cell populations in mice and applied the results to published TCR sequence data obtained from human patients. We screened peripheral blood T cells obtained monthly from individual mice spontaneously developing breast tumors by 5 months. We then looked at identical TCR sequences in published human studies; we used TCGA data from tumors and healthy tissues of 1,256 breast cancer resections and from 4 focused studies including sequences from tumors, lymph nodes, blood and healthy tissues, and from single cell dataset of 3 breast cancer subjects. We now report that mice spontaneously developing breast cancer manifest shared, Public CDR3 regions in both their alpha and beta and that a significant number of women with early breast cancer manifest identical CDR3 sequences. These findings suggest that the development of breast cancer is associated, across species, with biomarker, exclusive TCR repertoires.

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Section: Discussionmentioning

confidence: 99%

Breast cancer is marked by specific, Public T-cell receptor CDR3 regions shared by mice and humans

et al. 2021

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“…T cells are descendants of bone marrow progenitors that migrated to the thymus and underwent processes of maturation, gene rearrangement and selection (8). The surface of a T cell is populated with tens of thousands of copies of a T-cell receptor.…”

Section: Introductionmentioning

confidence: 99%

Fate of a Naive T Cell: A Stochastic Journey

et al. 2019

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The homeostasis of T cell populations depends on migration, division and death of individual cells (1). T cells migrate between spatial compartments (spleen, lymph nodes, lung, liver, etc.), where they may divide or differentiate, and eventually die (2). The kinetics of recirculation influences the speed at which local infections are detected and controlled (3). New experimental techniques have been developed to measure the lifespan of cells, and their migration dynamics; for example, fluorescence-activated cell sorting (4), in vitro time-lapse microscopy (5), or in vivo stable isotope labeling (e.g., deuterium) (6). When combined with mathematical and computational models, they allow estimation of rates of migration, division, differentiation and death (6, 7). In this work, we develop a stochastic model of a single cell migrating between spatial compartments, dividing and eventually dying. We calculate the number of division events during a T cell's journey, its lifespan, the probability of dying in each compartment and the number of progeny cells. A fast-migration approximation allows us to compute these quantities when migration rates are larger than division and death rates. Making use of published rates: (i) we analyse how perturbations in a given spatial compartment impact the dynamics of a T cell, (ii) we study the accuracy of the fast-migration approximation, and (iii) we quantify the role played by direct migration (not via the blood) between some compartments.

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“…28 They review statistical and heuristic models of diversity in the T-cell repertoire, but this is followed by a review of more mechanistic models of the biology of naive T cells from birth to maturity. 29 The various authors of the reviews in this issue tended to emphasize biology and biological implications of mathematical modeling in the various systems. We also asked them to include some details of the mathematical approaches used.…”

Section: Introductionmentioning

confidence: 99%

“…Such models and interpreting experimental results in this area are the topics of the review by Lythe & Molina‐Paris . They review statistical and heuristic models of diversity in the T‐cell repertoire, but this is followed by a review of more mechanistic models of the biology of naive T cells from birth to maturity . These models have been developed by integrating modeling and experiments to discover a better picture of the life history of T cells, in an exemplar long‐standing collaboration among the authors of that review.…”

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confidence: 99%