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Open Access Research article

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

Yonatan Savir13, Nir Waysbort2, Yaron E Antebi24, Tsvi Tlusty1 and Nir Friedman2*

Author affiliations

1 The Simons Center for Systems Biology, Institute for Advanced Studies, Princeton, New Jersey, 08540, USA

2 Department of Immunology, Weizmann Institute of Science, Rehovot, 76100, Israel

3 Department of Systems Biology,, Harvard Medical School Harvard Medical School, Warren Alpert Building, Room 555B 200 Longwood Avenue, Boston, MA, 02115, USA

4 Division of Biology, Caltech, Pasadena, CA, 91125, USA

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Citation and License

BMC Systems Biology 2012, 6:111  doi:10.1186/1752-0509-6-111

Published: 27 August 2012

Abstract

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.

Keywords:
Systems immunology; Positive feedback; Speed vs. accuracy; IL-2; CD25