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Balancing speed and accuracy of polyclonal T cell activation: a role for extracellular feedback

Savir, Yonatan and Waysbort, Nir and Antebi, Yaron E. and Tlusty, Tsvi and Friedman, Nir (2012) Balancing speed and accuracy of polyclonal T cell activation: a role for extracellular feedback. BMC Systems Biology, 6 . Art. No. 111. ISSN 1752-0509. doi:10.1186/1752-0509-6-111.

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Background: Extracellular feedback is an abundant module of intercellular communication networks, yet a detailed understanding of its role is still lacking. Here, we study interactions between polyclonal activated T cells that are mediated by IL-2 extracellular feedback as a model system. Results: Using mathematical modeling we show that extracellular feedback can give rise to opposite outcomes: competition or cooperation between interacting T cells, depending on their relative levels of activation. Furthermore, the outcome of the interaction also depends on the relative timing of activation of the cells. A critical time window exists after which a cell that has been more strongly activated nevertheless cannot exclude an inferior competitor. Conclusions: In a number of experimental studies of polyclonal T-cell systems, outcomes ranging from cooperation to competition as well as time dependent competition were observed. Our model suggests that extracellular feedback can contribute to these observed behaviors as it translates quantitative differences in T cells’ activation strength and in their relative activation time into qualitatively different outcomes. We propose extracellular feedback as a general mechanism that can balance speed and accuracy – choosing the most suitable responders out of a polyclonal population under the clock of an escalating threat.

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Friedman, Nir0000-0002-9678-3550
Additional Information:© 2012 Savir et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 7 February 2012; Accepted: 2 August 2012; Published: 27 August 2012. We thank Uri Alon, Benjamin Chain, Ofer Feinerman, Ron Milo, Wilfred Ndifon and Jacob Rimer for helpful comments on the manuscript. This research was supported by The International Human Frontier Science Program Organization and by the Abisch-Frenkel Foundation. TT thanks the Simons Foundation, and Helen and Martin Chooljian for their generous support. TT is the Helen and Martin Chooljian Founders' Circle Member in the Simons Center for Systems Biology at the Institute for Advanced Studies, Princeton. NF is incumbent of the Pauline Recanati Career Development Chair of Immunology. Authors’ contributions: YS, NW, YEA, TT and NF designed the study; YS and NW performed the study; YEA contributed to early stages of this work; YS, NW and NF wrote the manuscript. All authors read and approved the final manuscript.
Funding AgencyGrant Number
International Human Frontier Science Program OrganizationUNSPECIFIED
Abisch-Frenkel FoundationUNSPECIFIED
Simons FoundationUNSPECIFIED
Subject Keywords:Systems immunology; Positive feedback; Speed vs. accuracy; IL-2; CD25
Record Number:CaltechAUTHORS:20130111-143231499
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Official Citation:Savir et al.: Balancing speed and accuracy of polyclonal T cell activation: a role for extracellular feedback. BMC Systems Biology 2012 6:111
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:36330
Deposited By: Tony Diaz
Deposited On:14 Jan 2013 22:52
Last Modified:09 Nov 2021 23:21

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