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Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin

Nature Immunology volume 6, pages 1236–1244 (2005)Cite this article

A Corrigendum to this article was published on 01 January 2006

This article has been updated

Abstract

Two seemingly unrelated hallmarks of memory CD8+ T cells are cytokine-driven proliferative renewal after pathogen clearance and a latent effector program in anticipation of rechallenge. Memory CD8+ T cells and natural killer cells share cytotoxic potential and dependence on the growth factor interleukin 15. We now show that mice with compound mutations of the genes encoding the transcription factors T-bet and eomesodermin were nearly devoid of several lineages dependent on interleukin 15, including memory CD8+ T cells and mature natural killer cells, and that their cells had defective cytotoxic effector programming. Moreover, T-bet and eomesodermin were responsible for inducing enhanced expression of CD122, the receptor specifying interleukin 15 responsiveness. Therefore, these key transcription factors link the long-term renewal of memory CD8+ T cells to their characteristic effector potency.

*Note: In the version of this article initially published online, the third sentence of the abstract was incorrect. The correct sentence is as follows: “We now show that mice with compound mutations of the genes encoding the transcription factors T-bet and eomesodermin were nearly devoid of several lineages dependent on interleukin 15, including memory CD8+ T cells and mature natural killer cells, and that their cells had defective cytotoxic effector programming.” The error has been corrected for the HTML and print versions of the article. Additionally, in the print version of this article and the version initially published online, some labels for Tbx21 in Figure 7b are incorrect. This correction has been appended to the PDF version.

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Figure 1: Eomes+/−Tbx21−/− mice have considerable depletion of IL-15-dependent lineages.
Figure 2: Eomes and T-bet are expressed in IL-15-dependent lineages.
Figure 3: T-box factors coincide with CD122 and IL-15 responsiveness.
Figure 4: Eomes and T-bet are necessary for the induction and maintenance of the CD122hi state.
Figure 5: Eomes and T-bet are sufficient to induce the CD122hi state.
Figure 6: Il2rb is a direct 'target' of Eomes.
Figure 7: Eomes and T-bet coordinate effector function in parallel with their coordination of IL-15 responsiveness.

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  • 13 November 2005

    Sentence in abstract changed. Also figure 7b.

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Acknowledgements

We thank E. Allenspach, A. Banerjee, M. Bogumil, T. Bui, J. Chang, C. DiCioccio, M. Gohil, I. Kinjyo, E. Meyers, Y. Ohtani, F. Schambach and J. Stundon for assistance and discussion; D. Garalde-Intlekofer for support. Supported by the National Institutes of Health (AI042370, AI061699 and AI007532) and the Abramson Family.

Author information

Author notes

  1. E John Wherry

    Present address: The Wistar Institute, Philadelphia, Pennsylvania, 19104, USA

  2. Susan M Kaech

    Present address: Yale University, New Haven, Connecticut, 06520, USA

  3. Ananda W Goldrath

    Present address: University of California, San Diego, La Jolla, California, 92093, USA

Authors and Affiliations

  1. Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Andrew M Intlekofer, Naofumi Takemoto, Sarah A Longworth, John T Northrup, Vikram R Palanivel, Alan C Mullen, Christopher R Gasink & Steven L Reiner

  2. Department of Pediatrics, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Kenneth Ryan & Jordan S Orange

  3. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Tullia Lindsten

  4. Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, 30322, Georgia, USA

    E John Wherry, Susan M Kaech, Joseph D Miller & Rafi Ahmed

  5. Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Science Center, Denver, 80206, Colorado, USA

    Laurent Gapin

  6. Department of Biochemistry, Genetics Unit, University of Oxford, Oxford, OX1 3QU, UK

    Andreas P Russ

  7. Joslin Diabetes Center and Department of Medicine, Section on Immunology and Immunogenetics, Brigham and Women's Hospital, Harvard Medical School, Boston, 02215, Massachusetts, USA

    Ananda W Goldrath

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Supplementary information

Supplementary Fig. 1

Intermediate NK and NKT cell defects in mice with less severe mutations of Tbx21 and Eomes. (PDF 261 kb)

Supplementary Fig. 2

Eomes and T-bet are expressed in endogenous memory CD8+ T cells that arise after viral infection. (PDF 131 kb)

Supplementary Fig. 3

Distinguishing basal CD122 expression from the CD122hi state among CD8+ cells. (PDF 95 kb)

Supplementary Fig. 4

IL-15 signaling is not required for enhanced induction of CD122. (PDF 119 kb)

Supplementary Fig. 5

T-bet and Eomes expression correlates with cytolytic effector molecule expression in human CD8+ cells. (PDF 131 kb)

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Intlekofer, A., Takemoto, N., Wherry, E. et al. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol 6, 1236–1244 (2005). https://doi.org/10.1038/ni1268

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