Nature 457, 557-561 (29 January 2009) | doi:10.1038/nature07665; Received 23 October 2008; Accepted 24 November 2008; Published online 11 January 2009

There is an Erratum (26 February 2009) associated with this document.

Adaptive immune features of natural killer cells

Joseph C. Sun1, Joshua N. Beilke1 & Lewis L. Lanier1

  1. Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, California 94143, USA

Correspondence to: Lewis L. Lanier1 Correspondence and requests for materials should be addressed to L.L.L. (Email:


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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