NK cells, traditionally considered part of the innate immune system, exhibit adaptive immune features such as proliferation, contraction, memory maintenance, and recall responses during viral infections. In a mouse model of cytomegalovirus (MCMV) infection, NK cells expressing the Ly49H receptor proliferate significantly in the spleen and liver following infection, similar to T cells. These NK cells undergo a contraction phase, then persist in lymphoid and non-lymphoid organs for several months as self-renewing "memory" NK cells. Upon reactivation, they rapidly degranulate and produce cytokines, leading to a robust secondary expansion and protective immunity when transferred into naive animals. This study reveals that NK cells possess novel properties previously attributed only to adaptive immune cells. Key genes and proteins involved include Ly49H, DAP12, m157, interferon-gamma, and NK1.1. During MCMV infection, naive T cells proliferate and generate memory T cells, which undergo contraction and then memory maintenance. NK cells follow a similar pattern, with memory NK cells persisting in tissues and responding to reactivation. The study shows that NK cells can expand and contract in response to infection, with memory NK cells maintaining a long-term presence and being able to respond to subsequent viral challenges. The research demonstrates that NK cells can undergo all four phases of an immune response: expansion, contraction, memory maintenance, and recall. Adoptive transfer of NK cells into DAP12-deficient mice shows that they can expand significantly in the spleen and liver, indicating their ability to proliferate and maintain memory. Memory NK cells are functionally active, producing IFN-γ and degranulating upon reactivation. They also exhibit phenotypic differences compared to naive NK cells, including higher expression of certain surface markers and increased IFN-γ production. The study also shows that memory NK cells can mount a secondary response upon viral challenge, expanding up to 100-fold in the spleen. When compared to naive NK cells, memory NK cells are more protective, as demonstrated by their ability to protect neonatal mice from MCMV infection. This suggests that NK cells can "remember" previously encountered pathogens and provide more efficient protective immunity against subsequent infections. The findings challenge the traditional classification of NK cells as purely innate immune cells and highlight their ability to undergo adaptive immune processes. This has implications for understanding immunological memory and could influence vaccination strategies. The study provides insights into the complex interplay between innate and adaptive immune systems, emphasizing the importance of NK cells in immune responses.NK cells, traditionally considered part of the innate immune system, exhibit adaptive immune features such as proliferation, contraction, memory maintenance, and recall responses during viral infections. In a mouse model of cytomegalovirus (MCMV) infection, NK cells expressing the Ly49H receptor proliferate significantly in the spleen and liver following infection, similar to T cells. These NK cells undergo a contraction phase, then persist in lymphoid and non-lymphoid organs for several months as self-renewing "memory" NK cells. Upon reactivation, they rapidly degranulate and produce cytokines, leading to a robust secondary expansion and protective immunity when transferred into naive animals. This study reveals that NK cells possess novel properties previously attributed only to adaptive immune cells. Key genes and proteins involved include Ly49H, DAP12, m157, interferon-gamma, and NK1.1. During MCMV infection, naive T cells proliferate and generate memory T cells, which undergo contraction and then memory maintenance. NK cells follow a similar pattern, with memory NK cells persisting in tissues and responding to reactivation. The study shows that NK cells can expand and contract in response to infection, with memory NK cells maintaining a long-term presence and being able to respond to subsequent viral challenges. The research demonstrates that NK cells can undergo all four phases of an immune response: expansion, contraction, memory maintenance, and recall. Adoptive transfer of NK cells into DAP12-deficient mice shows that they can expand significantly in the spleen and liver, indicating their ability to proliferate and maintain memory. Memory NK cells are functionally active, producing IFN-γ and degranulating upon reactivation. They also exhibit phenotypic differences compared to naive NK cells, including higher expression of certain surface markers and increased IFN-γ production. The study also shows that memory NK cells can mount a secondary response upon viral challenge, expanding up to 100-fold in the spleen. When compared to naive NK cells, memory NK cells are more protective, as demonstrated by their ability to protect neonatal mice from MCMV infection. This suggests that NK cells can "remember" previously encountered pathogens and provide more efficient protective immunity against subsequent infections. The findings challenge the traditional classification of NK cells as purely innate immune cells and highlight their ability to undergo adaptive immune processes. This has implications for understanding immunological memory and could influence vaccination strategies. The study provides insights into the complex interplay between innate and adaptive immune systems, emphasizing the importance of NK cells in immune responses.