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Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells

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  • Matthew A. Williams

    (University of Washington)

  • Aaron J. Tyznik

    (University of Washington)

  • Michael J. Bevan

    (University of Washington)

Abstract

Although interleukin-2 (IL-2) was initially characterized as the primary T-cell growth factor following in vitro activation1, less is known about its role in shaping T-cell responses to acute infections in vivo. The use of IL-2- or IL-2-receptor-deficient mice is problematic owing to their early development of autoimmunity2,3,4,5, attributable to the central role of IL-2 in the generation, maintenance and function of CD4+CD25+ regulatory T cells6,7,8,9. To bypass these inherent difficulties, we have studied the effect of IL-2 on T-cell responses to acute infections by adopting a mixed chimaera strategy in which T cells lacking the high-affinity IL-2 receptor could be studied in an otherwise healthy mouse containing a full complement of regulatory T cells. Here we show that although IL-2 signalling to pathogen-specific CD8+ T cells affects the number of developing effector and memory cells very little, it is required for the generation of robust secondary responses. This is not due to an altered T-cell-receptor repertoire development or selection, and does not reflect an acute requirement for IL-2 during secondary activation and expansion. Rather, we demonstrate a previously unappreciated role for IL-2 during primary infection in programming the development of CD8+ memory T cells capable of full secondary expansion. These results have important implications for the development of vaccination or immunotherapeutic strategies aimed at boosting memory T-cell function.

Suggested Citation

  • Matthew A. Williams & Aaron J. Tyznik & Michael J. Bevan, 2006. "Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells," Nature, Nature, vol. 441(7095), pages 890-893, June.
  • Handle: RePEc:nat:nature:v:441:y:2006:i:7095:d:10.1038_nature04790
    DOI: 10.1038/nature04790
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    Cited by:

    1. Shu Shien Chin & Erik Guillen & Laurent Chorro & Sooraj Achar & Karina Ng & Susanne Oberle & Francesca Alfei & Dietmar Zehn & Grégoire Altan-Bonnet & Fabien Delahaye & Grégoire Lauvau, 2022. "T cell receptor and IL-2 signaling strength control memory CD8+ T cell functional fitness via chromatin remodeling," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    2. Diane Maurice & Patrick Costello & Jessica Diring & Francesco Gualdrini & Bruno Frederico & Richard Treisman, 2024. "IL-2 delivery to CD8+ T cells during infection requires MRTF/SRF-dependent gene expression and cytoskeletal dynamics," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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