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      A cellular calculus for signal integration by T cells.

      Nature immunology
      Animals, Cell Count, Cell Division, immunology, Female, Fluoresceins, Fluorescent Dyes, Lymphocyte Activation, Mice, Models, Immunological, Normal Distribution, Signal Transduction, Succinimides, T-Lymphocytes

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          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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