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Killing of Targets by CD8+ T Cells in the Mouse Spleen Follows the Law of Mass Action

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  • Vitaly V Ganusov
  • Daniel L Barber
  • Rob J De Boer

Abstract

It has been difficult to correlate the quality of CD8 T cell responses with protection against viral infections. To investigate the relationship between efficacy and magnitude of T cell responses, we quantify the rate at which individual CD8 effector and memory T cells kill target cells in the mouse spleen. Using mathematical modeling, we analyze recent data on the loss of target cells pulsed with three different peptides from the mouse lymphocytic choriomeningitis virus (LCMV) in mouse spleens with varying numbers of epitope-specific CD8 T cells. We find that the killing of targets follows the law of mass-action, i.e., the death rate of individual target cells remains proportional to the frequency (or the total number) of specific CD8 T cells in the spleen despite the fact that effector cell densities and effector to target ratios vary about a 1000-fold. The killing rate of LCMV-specific CD8 T cells is largely independent of T cell specificity and differentiation stage. Our results thus allow one to calculate the critical T cell concentration at which growth of a virus with a given replication rate can be prevented from the start of infection by memory CD8 T cell response.

Suggested Citation

  • Vitaly V Ganusov & Daniel L Barber & Rob J De Boer, 2011. "Killing of Targets by CD8+ T Cells in the Mouse Spleen Follows the Law of Mass Action," PLOS ONE, Public Library of Science, vol. 6(1), pages 1-8, January.
    • Handle: RePEc:plo:pone00:0015959
    DOI: 10.1371/journal.pone.0015959
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    1. Jinyan Liu & Kara L. O’Brien & Diana M. Lynch & Nathaniel L. Simmons & Annalena La Porte & Ambryice M. Riggs & Peter Abbink & Rory T. Coffey & Lauren E. Grandpre & Michael S. Seaman & Gary Landucci & , 2009. "Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys," Nature, Nature, vol. 457(7225), pages 87-91, January.
    2. Frederik Graw & Roland R Regoes, 2009. "Investigating CTL Mediated Killing with a 3D Cellular Automaton," PLOS Computational Biology, Public Library of Science, vol. 5(8), pages 1-12, August.
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    Cited by:

    1. Claire Christophe & Sabina Müller & Magda Rodrigues & Anne-Elisabeth Petit & Patrick Cattiaux & Loïc Dupré & Sébastien Gadat & Salvatore Valitutti, 2015. "A Biased Competition Theory of Cytotoxic T Lymphocyte Interaction with Tumor Nodules," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-23, March.
    2. Victor Garcia & Kirsten Richter & Frederik Graw & Annette Oxenius & Roland R Regoes, 2015. "Estimating the In Vivo Killing Efficacy of Cytotoxic T Lymphocytes across Different Peptide-MHC Complex Densities," PLOS Computational Biology, Public Library of Science, vol. 11(5), pages 1-19, May.

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    2. Victor Garcia & Kirsten Richter & Frederik Graw & Annette Oxenius & Roland R Regoes, 2015. "Estimating the In Vivo Killing Efficacy of Cytotoxic T Lymphocytes across Different Peptide-MHC Complex Densities," PLOS Computational Biology, Public Library of Science, vol. 11(5), pages 1-19, May.

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