Adaptive Immune Features of Natural Killer Cells

By Joseph C. Sun, J. Beilke, L. Lanier. Nature, 2009

1,606 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/1a489ee852fa1d47e7cbab0d78f122749f7a8e8f

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In Immunology

1. Joseph C. Sun
2. Bali Pulendran
3. C. A. Dinarello
4. M. Caligiuri
5. Rafi Ahmed
6. E. Latz
7. Eric O Long
8. M. Colonna

Citations in the corpus

• NK cell development, homeostasis and function: parallels with CD8+ T cells (2011, background): “In certain mouse strains (such as C57BL/6), LY49H + NK cells can undergo a 3- to 10-fold expansion in absolute numbers (measured in the spleen and liver) over the course of 6–7 days after viral infectio”
• Trained immunity: a program of innate immune memory in health and disease (2016, background): “In a study in patients recovering from CMV virus infection, the DNA methylation patterns of NK-cells and cytotoxic T-cells were similar, and very different from those of canonical NK cells.”
• The Transcription Factors T-bet and Eomes Control Key Checkpoints of Natural Killer Cell Maturation (2012, background): “…will be directed toward determining whether TRAIL+ and DX5+ NK cells kill targets in the same manner, whether both subsets are capable of memory responses, and whether effector memory cell functions are dependent on T-bet, Eomes, or both (Cooper et al., 2009; Paust et al., 2010; Sun et al., 2009).”
• Natural killer cells in cancer biology and therapy (2020, background): “However, in addition to beating tumor cells, the risk of long-lived NK cells should not be ignored where their “brake” is lost and they might also kill normal cells, even worse, finally increasing the possibilities of NK lymphoma [95, 238].”
• Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent anti-tumor activity (2017, neutral): “Although recent data support the existence of long-lived memory NK cells in mice (41, 42) and possibly in humans(43–45), the absence of a reliable and stable marker (or set of markers) to define memory NK cells hinders their selection for immunotherapy.”
• Modulation of natural killer cell activity by viruses (2010, positive): “More recent data indicate that NK cells may even acquire memory-like function enabling them to respond differently upon recall challenge [1 ,2 ,3].”
• Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity (2016, background): “…studies demonstrated that certain infections and vacci- nations induce innate immune memory (also termed trained im- munity; Netea et al., 2016) in monocytes, macrophages, and natural killer cells, resulting in non-specific protection against reinfection (Quintin et al., 2012; Sun et al., 2009).”
• Insect immune priming: ecology and experimental evidences (2016, background): “Immune priming has now been studied in vertebrates (Sun et al., 2009; Paust & von Andrian, 2011), invertebrates (Kurtz, 2005; Schmid-Hempel, 2011; Masri & Cremer, 2014), and plants (Spoel & Dong, 2012).”
• Pre-activation with IL-12, IL-15, and IL-18 induces CD25 and a functional high affinity IL-2 receptor on human cytokine-induced memory-like NK cells (2014, background): “However, this paradigm has recently been challenged by several groups identifying innate memory mediated by mouse NK cells [13] in the setting of hapten-based sensitization [14], viral (murine cytomegalovirus [MCMV]) infection [15], and after cytokine activation with IL-12, IL-15, and IL-18 [16].”
• Targeting natural killer cells and natural killer T cells in cancer (2012, background): “For example, NK cells use LY49H (also known as KLRA8) — a receptor that could be considered to be an invariant TCR-like receptor — to recognize the mouse cytomegalovirus (MCMV) protein m157, and they functionally behave as innate T cell”
• Bacille Calmette-Guérin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes (2012, background): “Indeed,murineCMV infection can induce protection from reinfection in aT/B-cell–independent and natural killer cell–dependent fashion (4, 32), and systemic infection with C.”
• Controlling NK Cell Responses: Integration of Signals for Activation and Inhibition (2013, background): “Mouse NK cells exhibit innate memory properties after infection with MCMV and vaccinia virus (140, 141).”
• Candida albicans Infection Affords Protection against Reinfection via Functional Reprogramming of Monocytes (2012, background): “Recently, NK cells, another prototypical type of innate immune cells, have been demonstrated to possess memory characteristics (O’Leary et al., 2006; Paust et al., 2010; Sun et al., 2009).”