What is natural in natural killer cells?

Denomination is a not a trivial issue in human activities in general, and in science in particular. Natural killer (NK) cells have been originally characterized as cytolytic effector lymphocytes present in mouse spleen and human peripheral blood. The "NK" name was originally coined after the NK cell's ability to kill targets cells without requirement for a prior exposure to these targets, in contrast to cytolytic T cells (Kiessling, R., Klein, E., Wigzell, H. 1975. "Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol 5:112-117). In this review, an attempt is made to revisit the basis for this vastly admitted definition of NK cells, and to enumerate some of the unsolved questions related to NK cell biology. An emphasis will be given to recent data showing that circulating NK cells are not steady state killers unless they have gone through a process of functional maturation. This process that is referred as to "NK cell education" thereafter involves self MHC class I recognition via inhibitory receptors, but also some still unidentified factors. Therefore, the NK denomination does not reflect a genuine property of these lymphocytes that appear to more and more resemble T and B lymphocytes.