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Molecular definition of the identity and activation of natural killer cells

Nature Immunology volume 13, pages 1000–1009 (2012)Cite this article

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Abstract

Using whole-genome microarray data sets of the Immunological Genome Project, we demonstrate a closer transcriptional relationship between NK cells and T cells than between any other leukocytes, distinguished by their shared expression of genes encoding molecules with similar signaling functions. Whereas resting NK cells are known to share expression of a few genes with cytotoxic CD8+ T cells, our transcriptome-wide analysis demonstrates that the commonalities extend to hundreds of genes, many encoding molecules with unknown functions. Resting NK cells demonstrate a 'preprimed' state compared with naive T cells, which allows NK cells to respond more rapidly to viral infection. Collectively, our data provide a global context for known and previously unknown molecular aspects of NK cell identity and function by delineating the genome-wide repertoire of gene expression of NK cells in various states.

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Figure 1: NK cells and T cells show close similarity at the transcriptome level.
Figure 2: Organization of the innate and adaptive branches of the NK cell–T cell complex.
Figure 3: Molecular uniqueness of resting NK cells.
Figure 4: Naive NK cells are primed for effector responses.
Figure 5: The response of Ly49H+ NK cells to MCMV infection is dominated by an early activation response, followed by effector and memory responses.
Figure 6: Common effector mechanisms of NK cells and CD8+ T cells.
Figure 7: Common memory responses of NK cells and CD8+ T cells.

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Acknowledgements

We thank A. Weiss (University of California, San Francisco) for antibody to Syk; the members of the ImmGen Consortium and M. Dozmorov for discussions; the ImmGen core team (M. Painter, J. Ericson and S. Davis) for data generation and processing; J. Jarjoura and J. Arakawa-Hoyt for assistance in cell sorting; A. Beaulieu, J. Karo and S. Madera for data from MCMV infection experiments; and eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project. Supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R24 AI072073 and R01 AI068129; T32AI060537 to D.W.H.; T32AI060536 to J.A.B.; and AI072117 to A.W.G.), the American Cancer Society (L.L.L. and N.A.B.), the Canadian Institutes of Health Research (G.M.-O.) and the Searle Scholars Program (J.C.S.).

Author information

Author notes

  1. Natalie A Bezman, Charles C Kim, Joseph C Sun and Charlie C Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, California, USA

    Natalie A Bezman, Gundula Min-Oo, Deborah W Hendricks, Yosuke Kamimura & Lewis L Lanier

  2. Division of Experimental Medicine, University of California, San Francisco, San Francisco, California, USA

    Charles C Kim

  3. Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Joseph C Sun

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

    J Adam Best & Ananda W Goldrath

  5. Icahn Medical Institute, Mount Sinai Hospital, New York, New York, USA

    Emmanuel L Gautier, Claudia Jakubzick, Gwendalyn J Randolph, Jennifer Miller, Brian Brown & Miriam Merad

  6. Department of Pathology & Immunology, Washington University, St. Louis, Missouri, USA

    Emmanuel L Gautier & Gwendalyn J Randolph

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

    Adam J Best, Jamie Knell & Ananda Goldrath

  8. Computer Science Department, Stanford University, Stanford, California, USA

    Vladimir Jojic, Daphne Koller & Taras Kreslavsky

  9. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Nadia Cohen, Patrick Brennan & Michael Brenner

  10. Broad Institute, Cambridge, Massachusetts, USA

    Tal Shay & Aviv Regev

  11. Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA

    Anne Fletcher, Kutlu Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra & Shannon Turley

  12. Department of Computer Science, Brown University, Providence, Rhode Island, USA

    Radu Jianu & David Laidlaw

  13. Department of Biomedical Engineering, Howard Hughes Medical Institute, Boston University, Boston, Massachusetts, USA

    Jim J Collins

  14. University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Kavitha Narayan, Katelyn Sylvia & Joonsoo Kang

  15. Department of Stem Cell and Regenerative Biology, Harvard University, and Program in Cellular and Molecular Medicine, Children's Hospital, Boston, Massachusetts, USA

    Roi Gazit & Derrick J Rossi

  16. Joslin Diabetes Center, Boston, Massachusetts, USA

    Francis Kim, Tata Nageswara Rao & Amy Wagers

  17. Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Susan A Shinton & Richard R Hardy

  18. Department of Medicine, Boston University, Boston, Massachusetts, USA

    Paul Monach

  19. Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, California, USA

    Charlie C Kim

  20. Department of Microbiology & Immunobiology, Division of Immunology, Harvard Medical School, Boston, Massachusetts, USA

    Tracy Heng, Michio Painter, Jeffrey Ericson, Scott Davis, Diane Mathis & Christophe Benoist

Authors
  1. Natalie A Bezman
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  2. Charles C Kim
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Consortia

The Immunological Genome Project Consortium

  • Emmanuel L Gautier
  • , Claudia Jakubzick
  • , Gwendalyn J Randolph
  • , Adam J Best
  • , Jamie Knell
  • , Ananda Goldrath
  • , Jennifer Miller
  • , Brian Brown
  • , Miriam Merad
  • , Vladimir Jojic
  • , Daphne Koller
  • , Nadia Cohen
  • , Patrick Brennan
  • , Michael Brenner
  • , Tal Shay
  • , Aviv Regev
  • , Anne Fletcher
  • , Kutlu Elpek
  • , Angelique Bellemare-Pelletier
  • , Deepali Malhotra
  • , Shannon Turley
  • , Radu Jianu
  • , David Laidlaw
  • , Jim J Collins
  • , Kavitha Narayan
  • , Katelyn Sylvia
  • , Joonsoo Kang
  • , Roi Gazit
  • , Derrick J Rossi
  • , Francis Kim
  • , Tata Nageswara Rao
  • , Amy Wagers
  • , Susan A Shinton
  • , Richard R Hardy
  • , Paul Monach
  • , Natalie A Bezman
  • , Joseph C Sun
  • , Charlie C Kim
  • , Lewis L Lanier
  • , Tracy Heng
  • , Taras Kreslavsky
  • , Michio Painter
  • , Jeffrey Ericson
  • , Scott Davis
  • , Diane Mathis
  •  & Christophe Benoist

Contributions

C.C.K. analyzed data; N.A.B. and J.C.S. sorted cell subsets, did follow-up experiments and analyzed data; G.M.-O., D.W.H. and Y.K. did experiments; J.A.B. and A.W.G. designed and did the T cell studies; and N.A.B., C.C.K., J.C.S. and L.L.L. designed studies and wrote the paper.

Corresponding author

Correspondence to Lewis L Lanier.

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The authors declare no competing financial interests.

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Supplementary Tables 1–5 and Notes 1–2 (PDF 3341 kb)

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Bezman, N., Kim, C., Sun, J. et al. Molecular definition of the identity and activation of natural killer cells. Nat Immunol 13, 1000–1009 (2012). https://doi.org/10.1038/ni.2395

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