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A cellular calculus for signal integration by T cells

Nature Immunology volume 1, pages 239–244 (2000)Cite this article

Abstract

During an immune response numerous receptor-mediated signals delivered to T cells direct their proliferation, survival and differentiation. Here, we describe a quantitative model and in vitro methods for assessing the “calculus” used by T cells to process these multiple signals. The model reveals how T cells convert independently received signals into linear additive effects on division times which, in turn, amplify T cell number exponentially. These results explain why so many ligands can each appear obligatory for T cell activation and argue for a re-examination of the two-signal theory as the basis for decisions between tolerance and activation.

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Figure 1: Measuring independent parameters of T cell proliferation: time to first division and division cycle time.
Figure 2: Costimulation reduces mean time to first division.
Figure 3: Additive effect of mixing signals from costimulation and cytokines.
Figure 4: Four-parameter model predicts total cell numbers.
Figure 5: Cell numbers predicted by four-parameter model varying μ td1 and b(>0).

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Acknowledgements

We thank A. Basten, A. Baxter, M. Davenport, B. Fazekas de St Groth and S. Tangye for suggestions on the manuscript, and J. Allison and B. Castle for providing reagents. We also acknowledge the former professor of mathematics at Padua University who taught us how to combine experiment and mathematics to determine the outcome of interacting independent forces. Supported by a postgraduate scholarship from the University of Sydney (to A.G.) and grants from the NHMRC and the Medical Foundation of the University of Sydney.

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Authors and Affiliations

  1. Immune Regulation Group, Medical Foundation of the University of Sydney, Centenary Institute of Cancer Medicine and Cell Biology , Newtown, Sydney, 2042, NSW , Australia

    Amanda V. Gett & Philip D. Hodgkin

  2. Institute for Research in Biomedicine, Via Vincenzo Vela 6, Bellinzona, 6500, Switzerland

    Amanda V. Gett

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Correspondence to Philip D. Hodgkin.

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Gett, A., Hodgkin, P. A cellular calculus for signal integration by T cells. Nat Immunol 1, 239–244 (2000). https://doi.org/10.1038/79782

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