A cellular calculus for signal integration by T cells.
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.
Gett
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AV
Immune Regulation Group, Medical Foundation, University of Sydney, Centenary Institute of Cancer Medicine and Cell Biology, Newtown, Sydney 2042 NSW, Australia.
Hodgkin
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D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000276:immunology; D005260:Female; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D016011:Normal Distribution; D015398:Signal Transduction / Q000276:immunology; D013388:Succinimides; D013601:T-Lymphocytes / Q000276:immunology*
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D005456:Fluorescent Dyes; D013388:Succinimides