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Transcriptional insights into the CD8+ T cell response to infection and memory T cell formation

Nature Immunology volume 14, pages 404412 (2013) | Download Citation

Abstract

After infection, many factors coordinate the population expansion and differentiation of CD8+ effector and memory T cells. Using data of unparalleled breadth from the Immunological Genome Project, we analyzed the CD8+ T cell transcriptome throughout infection to establish gene-expression signatures and identify putative transcriptional regulators. Notably, we found that the expression of key gene signatures can be used to predict the memory-precursor potential of CD8+ effector cells. Long-lived memory CD8+ cells ultimately expressed a small subset of genes shared by natural killer T and γδ T cells. Although distinct inflammatory milieu and T cell precursor frequencies influenced the differentiation of CD8+ effector and memory populations, core transcriptional signatures were regulated similarly, whether polyclonal or transgenic, and whether responding to bacterial or viral model pathogens. Our results provide insights into the transcriptional regulation that influence memory formation and CD8+ T cell immunity.

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Acknowledgements

We thank eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project. Supported by the US National Institutes of Health (AI072117 and AI067545 to A.W.G.; T32 AI060536 to J.A.B.; PN2 EY016586 to D.A.B. and M.L.D.; P30 CA016087 for cell sorting; and R24 AI072073 (National Institute of Allergy and Infectious Diseases) to the ImmGen Consortium), the Pew Scholars program (A.W.G.) and the Cancer Research Institute (A.W.G. and V.M.).

Author information

Affiliations

  1. Division of Biological Sciences, University of California San Diego, La Jolla, California, USA.

    • J Adam Best
    • , Jamie Knell
    • , Edward Yang
    • , Andrew Doedens
    •  & Ananda W Goldrath
  2. Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA.

    • David A Blair
    • , Viveka Mayya
    •  & Michael L Dustin
  3. Department of Medicine, Boston University, Boston, Massachusetts, USA.

    • Paul Monach
  4. Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

    • Susan A Shinton
    •  & Richard R Hardy
  5. Computer Science Department, Brown University, Providence, Rhode Island, USA.

    • Radu Jianu
    •  & David Koller
  6. Department of Biomedical Engineering, Howard Hughes Medical Institute, Boston University, Boston, Massachusetts, USA.

    • Jim Collins
  7. Immune Diseases Institute, Children's Hospital, Boston, Massachusetts, USA.

    • Roi Gazit
    • , Brian S Garrison
    •  & Derrick J Rossi
  8. Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

    • Kavitha Narayan
    • , Katelyn Sylvia
    •  & Joonsoo Kang
  9. Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.

    • Anne Fletcher
    • , Kutlu Elpek
    • , Angelique Bellemare-Pelletier
    • , Deepali Malhotra
    •  & Shannon Turley
  10. Computer Science Department, Stanford University, Stanford, California, USA.

    • Vladimir Jojic
    •  & Daphne Koller
  11. Broad Institute, Cambridge, Massachusetts, USA.

    • Tal Shay
    •  & Aviv Regev
  12. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Nadia Cohen
    • , Patrick Brennan
    • , Michael Brenner
    •  & Taras Kreslavsky
  13. Department of Microbiology & Immunology, University of California San Francisco, San Francisco, California, USA.

    • Natalie A Bezman
    • , Joseph C Sun
    • , Charlie C Kim
    •  & Lewis L Lanier
  14. Icahn Medical Institute, Mount Sinai Hospital, New York, New York, USA.

    • Jennifer Miller
    • , Brian Brown
    • , Miriam Merad
    • , Emmanuel L Gautier
    • , Claudia Jakubzick
    •  & Gwendalyn J Randolph
  15. Department of Pathology & Immunology, Washington University, St. Louis, Missouri, USA.

    • Emmanuel L Gautier
    •  & Gwendalyn J Randolph
  16. Joslin Diabetes Center, Boston, Massachusetts, USA.

    • Francis Kim
    • , Tata Nageswara Rao
    •  & Amy Wagers
  17. Division of Immunology, Department of Microbiology & Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

    • Tracy Heng
    • , Michio Painter
    • , Jeffrey Ericson
    • , Scott Davis
    • , Ayla Ergun
    • , Michael Mingueneau
    • , Diane Mathis
    •  & Christophe Benoist

Consortia

  1. The Immunological Genome Project Consortium

    A list of members and affiliations appears at the end of the paper.

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Contributions

J.A.B. did experiments, designed studies, analyzed data and wrote the manuscript; J.K. sorted cell subsets and analyzed data; A.D. analyzed data and edited the manuscript; D.A.B., V.M. and M.L.D. designed and did early infection experiments, analyzed data and contributed to writing the manuscript; E.Y. sorted cell subsets; and A.W.G. designed studies, analyzed data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ananda W Goldrath.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–7, Tables 2–4 and Note

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    Supplementary Table 1

    Gene expression values for gene lists defined by clusters I-X.

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DOI

https://doi.org/10.1038/ni.2536

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