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.