Historical overview on the morphological characterization of large granular lymphocytes/natural killer cells

•Natural Killer (NK) cells correspond to the large granular lymphocytes (LGLs).•More than 90% of NK cells are found in the blood circulation.•NK cells exert cytotoxic functionsdirected against virus-infected cells and tumor cells.•Most NK cells have LGL morphological aspects.•Not all NK cells have LGL morphology and not all LGL cells are NK cells.

Natural Killer (NK) cells were discovered when research on T cells produced an unexplained background, or “natural” cytotoxicity in non-immunized mice. The previously unknown cells were thus named “natural” killer cells, or NK cells. They are roughly defined by a lack of the T cell marker CD3 and a presence of CD56 (or NCAM, neural cell adhesion molecule) and correspond to the large granular lymphocytes (LGLs). This article is focused to the description the morphological features of these cells and of the LGLs and to the fundamental contribution of the Italian scientist Carlo E. Grossi to the ultrastructural characterization of these cells.