Molecular definition of the identity and activation of natural killer cells

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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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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.).

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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.

Correspondence to Lewis L Lanier.

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