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Adaptive immune features of natural killer cells

An Erratum to this article was published on 26 February 2009


In an adaptive immune response, naive T cells proliferate during infection and generate long-lived memory cells that undergo secondary expansion after a repeat encounter with the same pathogen. Although natural killer (NK) cells have traditionally been classified as cells of the innate immune system, they share many similarities with cytotoxic T lymphocytes. We use a mouse model of cytomegalovirus infection to show that, like T cells, NK cells bearing the virus-specific Ly49H receptor proliferate 100-fold in the spleen and 1,000-fold in the liver after infection. After a contraction phase, Ly49H-positive NK cells reside in lymphoid and non-lymphoid organs for several months. These self-renewing ‘memory’ NK cells rapidly degranulate and produce cytokines on reactivation. Adoptive transfer of these NK cells into naive animals followed by viral challenge results in a robust secondary expansion and protective immunity. These findings reveal properties of NK cells that were previously attributed only to cells of the adaptive immune system.

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Figure 1: Preferential expansion of wild-type, but not DAP12-deficient, NK cells during MCMV infection.
Figure 2: Robust proliferation of adoptively transferred wild-type NK cells in DAP12-deficient mice after MCMV infection.
Figure 3: Expansion and contraction of NK cells in lymphoid and non-lymphoid tissues results in ‘memory’ NK cells.
Figure 4: Function and phenotype of ‘memory’ NK cells.
Figure 5: Secondary expansion and protective immunity in ‘memory’ NK cells.


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We thank the Lanier laboratory for comments and discussions, and R. Locksley and W. Seaman for critical reading of this manuscript. The work was supported by National Institutes of Health grant AI068129. J.C.S. is supported by the Irvington Institute for Immunological Research. J.N.B. is supported by the Juvenile Diabetes Research Foundation. L.L.L. is an American Cancer Society Research Professor.

Author Contributions J.C.S. and J.N.B. contributed to project planning, experimental work, data analysis and writing the manuscript. L.L.L. contributed to project planning, data analysis and writing the manuscript.

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Correspondence to Lewis L. Lanier.

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Sun, J., Beilke, J. & Lanier, L. Adaptive immune features of natural killer cells. Nature 457, 557–561 (2009).

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