NK Cell Biology — Abundant Receptors and the Balance Between Immune Self-Tolerance and Immune Surveillance
Natural killer (NK) cells are a specific type of lymphocyte considered part of innate immunity, accounting for 10% to 15% of total lymphocytes. They play a crucial role in immune surveillance of malignant cells and virus-infected cells [1] . NK cells mainly function through cytotoxicity: inducing apoptosis by secreting perforin/granzyme to produce "natural" cytotoxicity, and factors such as FasL ( ligand of Fas receptor, or CD95, tumor necrosis factor ) or TRAIL ( TNF-related apoptosis-inducing ligand ), which induces apoptosis through activation of death receptors; and antibody-dependent cellular cytotoxicity ( ADCC ) mediated by the Fc receptor CD16 ( FcγRIII ).
In addition, NK cells produce many cytokines, most notably interferon gamma and TNFα. Due to its excellent lytic ability and preactivation in an antigen-independent manner, the probability of causing adverse reactions is low . In fact, NK cell activity is regulated by a complex integration of activating and inhibitory signals—the sum of interactions between numerous receptors on their surface and different ligands on the surface of target cells (Figure 1 ) .
NK cells are composed of two subpopulations, CD56 dim and CD56 bright NK cells , which are defined by the intensity of their CD56 expression. CD56 dim cells account for approximately 90% of blood NK cells, are highly cytotoxic, and mainly express CD16. CD56 bright NK cells account for 10% of NK cells in circulating blood, but are mainly found in lymph nodes and some other organs. They have lower CD16 expression and lower cytotoxicity than CD56 dim, but have strong proliferation potential. These differences in properties and functions are important to enhance the use and manipulation of NK cells in cell therapy.
NK cell cytotoxicity: balance between activation and inhibition.
Key Questions Answered
- What are natural killer (NK) cells and what is their primary function?
- Natural killer (NK) cells are a type of lymphocyte, constituting 10% to 15% of total lymphocytes, and are considered part of innate immunity. They play a crucial role in the immune surveillance of malignant cells and cells infected with viruses. NK cells primarily function through cytotoxicity, inducing apoptosis by secreting perforin/granzyme and factors like FasL or TRAIL, and through antibody-dependent cellular cytotoxicity (ADCC) mediated by the Fc receptor CD16.
- How do NK cells identify and eliminate target cells?
- NK cells function through cytotoxicity, which involves inducing apoptosis by secreting perforin/granzyme to produce "natural" cytotoxicity, or by using factors like FasL or TRAIL to activate death receptors. They also mediate antibody-dependent cellular cytotoxicity (ADCC) through the Fc receptor CD16. NK cell activity is regulated by a complex integration of activating and inhibitory signals from numerous receptors on their surface interacting with ligands on target cells.
- What are the different types of NK cells and their characteristics?
- NK cells are composed of two subpopulations: CD56 dim and CD56 bright NK cells. CD56 dim cells account for about 90% of blood NK cells, are highly cytotoxic, and primarily express CD16. CD56 bright NK cells make up 10% of circulating blood NK cells, are mainly found in lymph nodes, have lower CD16 expression and cytotoxicity than CD56 dim, but possess strong proliferation potential.
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