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T cell fitness determined by signal strength

Nature Immunology volume 4, pages 355–360 (2003)Cite this article

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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Figure 1: Duration and strength of stimulation determine T cell survival and cytokine responsiveness.
Figure 2: Prolonged interactions with mature DCs promote T cell fitness.
Figure 3: T cell fitness is associated with enhanced cytokine receptor expression and a high Bcl-xL to mitochondria ratio.
Figure 4: Strength of stimulation primes T cells for expansion or deletion in vivo.

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Acknowledgements

We thank P. Dellabona for OT-I mice; K. Karjalainen for critical reading and discussion; D. Jarossay for cell sorting; and L. Perlini and G. Bosshard for technical assistance. Supported by the European Community (contract QLK-CT-201-0105), the Swiss National Science Foundation (grant 31-63885) and the Helmut Horten Foundation (to A.L.).

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  1. Institute for Research in Biomedicine, Via Vela 6, Bellinzona, CH-6500, Switzerland

    Amanda V. Gett, Federica Sallusto, Antonio Lanzavecchia & Jens Geginat

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Correspondence to Antonio Lanzavecchia or Jens Geginat.

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Gett, A., Sallusto, F., Lanzavecchia, A. et al. T cell fitness determined by signal strength. Nat Immunol 4, 355–360 (2003). https://doi.org/10.1038/ni908

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