The biology of human natural killer cells

The human natural killer (NK) cell has long been known to mediate spontaneous, non-major histocompatibility complex-restricted cytotoxicity and antibody-dependent cellular cytotoxicity. It is only fairly recently, however, that the role NK cells play in other functions of the immune system has been realized. The NK cell participates either directly or indirectly in multiple developmental, regulatory and communication networks of the immune system and thus is important in human health and disease. The NK cell has distinct morphologic, phenotypic and ultrastructural characteristics that distinguish it from T and B lymphocytes. Human NK cells are heterogeneous, and functionally different subpopulations of NK cells can be distinguished. NK activity may be regulated by soluble products of hematopoietic as well as non-hematopoietic cells and by a wide variety of exogenous biological response modifiers. Both lymphocytes and monocytes are capable of regulating of NK cell growth and activity. Populations enriched in human NK cells can be obtained utilizing the property of adherence to plastic and subsequent expansion in the presence of IL-2. The adherent lymphokine activated killer (A-LAK) cells represent populations of CD3-CD56+ (up to 98%) IL-2 activated NK cells. They are highly effective in eliminating tumor cells both in vitro and in vivo in animal models of tumor metastasis. A-LAK cells are being used for therapy in the phase I clinical trial in patients with metastatic melanoma and renal cell carcinoma. The studies described emphasize the biologic importance of the NK cell, its therapeutic potential, and a need for more extensive monitoring of NK activity in human disease.