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Updated: Aug 14, 2026

Real-time Live Imaging of T-cell Signaling Complex Formation
Published on: June 23, 2013
T cell fitness determined by signal strength
Amanda V Gett1, Federica Sallusto, Antonio Lanzavecchia
1Institute for Research in Biomedicine, Via Vela 6, CH-6500 Bellinzona, Switzerland.
Abstract:
Two potential outcomes confront proliferating antigen-stimulated naive T cells: differentiation to effector and memory cells, or deletion. How stimulation affects cell fate is unclear. Autonomous CD8+ T cell differentiation has been proposed, but this does not explain the abortive proliferation of T cells induced by immature dendritic cells. Here we show that human and mouse CD4+ and CD8+ T cells receiving short or weak stimulation of the T cell receptor proliferate in response to interleukin 2 (IL-2) but are not 'fit' because they die by neglect, fail to proliferate in response to IL-7 and IL-15 and disappear in vivo. Conversely, prolonged or strong stimulation promotes 'fitness' by enhancing survival and cytokine responsiveness. Our results are consistent with the concept that signal strength drives progressive T cell differentiation and the acquisition of fitness.
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