Natural Killer Cells

Natural killer (NK) cells comprise about 10-15% of peripheral blood lymphocytes in adults (15). They are also numerous in the spleen but not in peripheral lymph nodes. Small numbers of NK cells are present in the liver, lung, and intestinal mucosa. Natural killer cells are cytotoxic cells which have the morphology of medium- to large-sized granular lymphocytes. The cytoplasmic granules contain phospholipids, proteoglycans, and cytotoxic proteins such as granzyme B and perforin (16). Natural killer cells do not rearrange any of the genes encoding the T-cell receptor chains nor express on their surface the CD3 antigen complex. Instead they express the FcyRIIA (CD16) and N-CAM (CD56) antigens (17). Cytotoxicity mediated by NK cells is non-MHC-restricted (18). Natural killer cells are capable of killing a variety of cell types, including tumor cells, virus-infected cells, and, in some instances, normal cells in the absence of previous deliberate or known sensitization. Natural killer cells interact with nonclassic MHC-I related molecules through inhibitory and activation receptors to identify targets for autologous killing (19). In this capacity, NK cells play a central role in the immune response to certain tumors. Natural killer cells are potent producers of interferon-gamma (IFN-y) and granulocyte macrophage colony stimulating factor (GM-CSF), and are capable of producing other cytokines, including tumor necrosis factor-alpha (TNF-a) (32). Natural killer cells stimulated by micro-organisms or by cytokines, such as IL-12 and TNF, produce large amounts of IFN-y and other cytokines that facilitate helper T-cell development.

Natural killer cells originate in the bone marrow from a common lymphoid precursor that gives rise to T, B, and NK cells (20). The cytokine IL-15 is particularly important in the differentiation and expansion of NK cells (21). Natural killer cell development is independent of the thymus.

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