CELLS

Natural killer (NK) cells, representing 5–20% of circulating lymphocytes, are the predominant innate lymphocyte subsets that mediate antitumor and antiviral responses. Earlier it was believed that NK cells develop only within the bone marrow; however, it has now been demonstrated that the development and maturation of NK cells may also take place in the secondary lymphoid tissues such as tonsils, spleen, and lymph nodes. The development of NK cells in the bone marrow and lymph nodes can be classified into six distinct stages (stages 1–6).¹

NK cells do not require prior antigen exposure to mediate their effector functions;¹ however, after activation, they secrete several cytokines such as IFN-γ, TNF-α, GM-CSF, IL-10, IL-5, and IL-13 and chemokines such as MIP-1α, MIP-1β, IL-8, and RANTES, that can modulate the function of other innate and adaptive immune cells.² IL-10 and IL-18 together have the potential to induce NK cell proliferation, cytotoxic function, and IFN-γ production. The cytokines secreted by NK cells significantly boost the antitumor immunity.²

In addition to their antitumor and antiviral functions, NK cells also mediate regulatory functions of myeloid or lymphoid cells by producing cytokines or via direct cell-cell contact in a receptor-ligand interaction-dependent manner.¹ Though typically considered to be a part of the innate immune system, NK cells also possess memory cell–like features.²

​​GM-CSF: granulocyte-macrophage colony-stimulating factor; IFN-γ: interferon gamma; IL: interleukin; MIP: macrophage inflammatory protein; RANTES: regulated on activation, normal T cell expressed and secreted; TNF: tumor necrosis factor.