Human natural killer cells: Their origin, receptors and function

The term of "natural killer" (NK) cells was originally assigned on a merely functional basis to lymphoid cells capable of lysing certain tumors in the absence of prior stimulation. However, both their origin and the molecular mechanism(s) involved in their function remained a mystery for many years [1]. Regarding their origin, clear evidence has now been provided both in mouse and in man that NK and T cells may derive from a common precursor [2-5]. Thus, mature NK cells can be obtained in vitro from CD34⁺ cells isolated from umbilical cord blood, bone marrow (BM) and even human thymus [6] when cultured in the presence of appropriate feeder cells or IL-15. The molecular mechanism allowing NK cells to discriminate between normal and tumor cells, predicted by the "missing self hypothesis" [7], has been clarified only in recent years. Thus, NK cells recognize MHC class I molecules through surface receptors delivering signals that inhibit, rather than activate, NK cells. As a consequence, NK cells lyse target cells that have lost (or express insufficient amounts of) MHC class I molecules, as frequently occurs in tumors and in cells infected by certain viruses.