Development and tolerance of natural killer cells

A natural killer (NK)/T cell-restricted progenitor cell in the fetal blood, with a phenotype of NK1.1+ CD117 (c-kit)+, can give rise to NK cells. IL-15 is probably required for NK cell differentiation and, in addition, stimulates expression of at least one of the MHC-specific inhibitory receptor families expressed by NK cells. Evidence supports the role of multiple mechanisms in rendering NK cells self tolerant — including selection for expression of self-specific inhibitory receptors, anergy and modulation of the cell surface levels of MHC-specific inhibitory receptors.