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Adaptive immune features of natural killer cells

2009; Nature Portfolio; Volume: 457; Issue: 7229 Linguagem: Inglês

10.1038/nature07665

1476-4687

Joseph C. Sun, Joshua Beilke, Lewis L. Lanier,

Reproductive System and Pregnancy

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. Recent evidence has suggested that like the cytotoxic T lymphocytes of the adaptive immune system, the natural killer (NK) cells traditionally seen as part of the innate immune system also have an immunological memory. This is now confirmed in experiments in a physiological setting — the virus-specific response of NK cells during a mouse cytomegalovirus infection. NK cells proliferated 1,000-fold in spleen and liver following the initial infection; the cells remained in the immune system for months and also conferred viral resistance when injected into other mice. This is of relevance to vaccine design and to work on the relationship between adaptive immunity and the evolutionarily older innate immunity. Recent evidence has suggested the existence of immunological memory in natural killer (NK) cells. This paper confirms and extends the earlier observation, providing direct evidence that memory NK cells are more effective than naive NK cells in controlling viral infection in vivo.