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