Adaptive immune features of natural killer cells

Joseph C. Sun, Joshua N. Beilke & Lewis L. Lanier. 2009. Nature. 457, 557-561

Speaker: Yi-Chun Chen (陳逸純)                                      Time: 13:00~14:00, Apr 8, 2009

Commentator: Dr. Li-Jin Hsu (徐麗君 老師)                Place: Room 601

Abstract:

Traditionally, natural killer (NK) cells are classified as part of the innate immune system. However, the authors  showed that natural killer cells also have memory properties previously described similar to T and B cells. In this study, a well-established model in which NK cells are known to confer protection by expressing virus-specific receptor Ly49H for murine cytomegalovirus (MCMV) resistance was used to determine NK cells-mediated immune response. There are four phases, including expansion phase,contraction phase, memory phase, and recall phase, are ascribed to adaptive immune cells.  To examine the expansion phase of the NK cell response, they transferred Ly49H+ NK cells into DAP12-deficient mice that lack functional Ly49H) and then found that these cells can proliferate extensively, specifically in response to MCMV. In addition, the authors also observed a contraction phase following the expansion of the NK-cell population after MCMV infection. The authors then investigated whether the expanded NK cell population was functional. They showed that the expanded NK cells produced high levels of interferon-gamma ex vivo following reactivation and termed “memory NK cells”. Finally, the authors examined whether memory NK cells could also undergo a secondary expansion phase. Indeed, an expanded memory Ly49H+ NK cell population was readily detectable following adoptive transfer into DAP12-deficient mice that were subsequently infected with MCMV. Importantly, memory Ly49H⁺ NK cells conferred higher levels of protection from MCMV infection when transferred into newborn mice than naive Ly49H+ NK cells. This study indicates that, similarly to antigen-specific T cells, memory NK cells can confer high levels of protection from a subsequent infection with the same pathogen. This study highlights that NK cells have traits of both innate and adaptive immune cells, questioning the concept of NK cells being solely innate immune cells.

References:

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2.      Arase, H. et al. 2002. Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296, 1323–1326