Fc Receptors on Mouse Effector Cells Mediating Natural Cytotoxicity Against Tumor Cells

Abstract

Mouse effector cells mediating natural cytotoxicity against tumor cells have been previously thought to be lymphocytes that lack any detectable cell surface markers. The present study presents evidence for receptors for the Fc portion of IgG on these cells. By adsorption of cytotoxic spleen cells on monolayers of sheep erythrocytes (E) plus IgG antibodies to sheep erythrocytes (EA), 50 to 96% of the total cytotoxic reactivity could be removed. Parallel adsorption of cells on E monolayers or on EA monolayers coated with protein A, to block the Fc portion of IgG, resulted in little or no depletion of cytotoxic activity. The presence of Fc receptors on the NK cells was confirmed by combining EA rosette formation with velocity sedimentation at unit gravity. Peak cytotoxicity occurred at the same sedimentation velocity as the peak of Fc-positive cells. After EA rosette formation, there was a shift to a higher sedimentation velocity in the Fc-positive cells and in the natural cytotoxic activity. The increase in sedimentation velocity of NK activity that was observed in these experiments indicated that most of the cells had only bound a small number (three or four) of antibody-coated erythrocytes. Together, these data indicate that cells with Fc receptors account for most of the total lytic activity of normal mouse spleen cells.

Mapping the chemotactic landscape in NK cells reveals subset-specific synergistic migratory responses to dual chemokine receptor ligation

“… 1 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 One important mode of target recognition is mediated by the FcγRIII (CD16) triggering antibody-dependent cellular cytotoxicity (ADCC). 12 , 13 NK cells can kill transformed or infected cells by the release of perforin and granzymes or by utilizing effector molecules of the tumor necrosis factor (TNF) family, such as TNF, TNF-related apoptosis-inducing ligand (TRAIL), and Fas ligand (FasL). 14 , 15 , 16 Additionally, upon activation, NK cells rapidly produce chemokines and cytokines, including interferon (IFN)-γ, and GM-CSF, that recruit and affect the function of hematopoietic and non-hematopoietic cells in the tumor microenvironment.…”