NK cell and endothelial cell interactions

Natural killer (NK) cells are a small subset of lymphocytes that represent critical effector cells of innate immunity as they are endowed with the ability to mediate cytotoxic activity and to secrete a variety of cytokines and chemokines. NK cells' prompt response, without the need for prior activation, represents a first line of defence against microbial infections, early cellular transformation and tumor growth as well as bone marrow transplantation. Moreover, accumulating evidences indicate that NK cells, by interacting with many cellular components of the immune system, play a crucial role also in the instruction and modulation of adaptive immune responses. NK cells develop from a lymphoid precursor resident in the bone marrow that is considered the main site of their generation, even if final maturation of NK cell precursors can occur also in the periphery. Mature NK cells predominantly circulate in the peripheral blood but are also resident in several lymphoid and non-lymphoid organs, such as the spleen, tonsils, lymph nodes, liver, lungs and intestine. In a steady state condition, the density of lymph node NK cells is higher in the medulla than in T-cell or B-cell areas, and the NK cells are mainly located within lymphatic sinuses. Among the non-lymphoid organs, the liver and uterus are selectively enriched in NK cells. Liver NK cells have been originally defined as PIT cells based on their spherical dense granules in the cytoplasm and rod-cored vesicles. Tissue-resident NK cells have many functions, including cytotoxicity or cytokine release, influencing the recruitment and activation of other leukocytes and also affecting vessel behavior.