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Clonally diverse T cell homeostasis is maintained by a common program of cell-cycle control

Описание

Тип публикации: статья из журнала

Год издания: 2013

Идентификатор DOI: 10.4049/jimmunol.1203213

Ключевые слова: lymphocyte antigen, animal cell, animal experiment, article, cell clone, cell cycle regulation, cell division, cell type, cellular parameters, controlled study, homeostasis, in vivo study, lymphocyte count, lymphocyte differentiation, lymphocyte proliferation, lymphocytopenia, mathematical model, mouse, nonhuman, prediction, priority journal, stochastic model, T lymphocyte, Adoptive Transfer, Animals, Cell Cycle, Cell Differentiation, Cell Line, Clone Cells, Immunophenotyping, Lymphocyte Activation, Lymphopenia, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Models, Immunological, Receptors, Antigen, T-Cell, T-Lymphocyte Subsets

Аннотация: Lymphopenia induces T cells to undergo cell divisions as part of a homeostatic response mechanism. The clonal response to lymphopenia is extremely diverse, and it is unknown whether this heterogeneity represents distinct mechanisms of cell-cycle control or whether a common mechanism can account for the diversity. We addressed this Показать полностьюquestion by combining in vivo and mathematical modeling of lymphopenia-induced proliferation (LIP) of two distinct T cell clonotypes. OT-I T cells undergo rapid LIP accompanied by differentiation that superficially resembles Ag-induced proliferation, whereas F5 T cells divide slowly and remain naive. Both F5 and OT-I LIP responses were most accurately described by a single stochastic division model where the rate of cell division was exponentially decreased with increasing cell numbers. The model successfully identified key biological parameters of the response and accurately predicted the homeostatic set point of each clone. Significantly, the model was successful in predicting interclonal competition between OT-I and F5 T cells, consistent with competition for the same resource(s) required for homeostatic proliferation. Our results show that diverse and heterogenous clonal T cell responses can be accounted for by a single common model of homeostasis. Copyright © 2013 by The American Association of Immunologists, Inc.

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Издание

Журнал: Journal of Immunology

Выпуск журнала: Vol. 190, Is. 8

Номера страниц: 3985-3993

Персоны

  • Hogan T. (Institute of Child Health, University College London, London, WC1N 1EH, United Kingdom, Division of Immune Cell Biology, Medical Research Council National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom)
  • Shuvaev A. (INSERM U897, Institut de Sant? Publique, d'?pid?miologie et de D?veloppement, Universit? Bordeaux Segalen, Bordeaux 33076, France, Institute of Fundamental Preparation, Siberian Federal University, Krasnoyarsk, Russian Federation)
  • Commenges D. (INSERM U897, Institut de Sant? Publique, d'?pid?miologie et de D?veloppement, Universit? Bordeaux Segalen, Bordeaux 33076, France)
  • Yates A. (Albert Einstein College of Medicine, Bronx, NY 10461, United States)
  • Callard R. (Institute of Child Health, University College London, London, WC1N 1EH, United Kingdom)
  • Thiebaut R. (INSERM U897, Institut de Sant? Publique, d'?pid?miologie et de D?veloppement, Universit? Bordeaux Segalen, Bordeaux 33076, France)
  • Seddon B. (Division of Immune Cell Biology, Medical Research Council National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom)

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