Direct evidence that natural killer cells in nonimmune spleen cell populations prevent tumor growth in vivo

Abstract
Relatively large numbers of nonimmune spleen cells did not protect against the local growth of 2 lymphomas. This heterogeneous population of splenic lymphocytes contained a subset of cells that efficiently protected against in vivo tumor growth. This cell population (cell-surface phenotype Thy1.2-Ig-Ly5.1+) represented < 5% of the spleen cell population and was responsible for in vitro NK[natural killer]-mediated lysis. These studies clearly and directly demonstrated that Ly5+ NK cells selected from a heterogeneous lymphoid population from nonimmune mice can protect syngeneic mice against local in vivo growth of 2 different types of tumor cells (in contrast to other lymphocyte sets within the spleen); they did not directly bear upon the role of NK cells in immunosurveillance. Highly enriched Ig[immunoglobulin]-Thy1-Ly5+ cells, which account for virtually all in vitro NK activity, can apparently retard tumor growth in vivo. It is difficult to ascribe all anti-tumor surveillance activity to NK cells, because they probably do not recirculate freely throughout the various organ systems of the body. NK cells may play a role in prevention of neoplastic growth within discrete anatomic compartments where there is rapid differentiation of stem cells to mature progeny (e.g., bone marrow, spleen and portions of the gastrointestinal tract) and may normally act to regulate the growth and differentiation of non-neoplastic stem cells. Long-term observation of chimeric mice repopulated with bone marrow from congenic or mutant donors expressing very low or very high NK activity may provide more answers.