Suppressor cells of the human NK activity: characterization of the cells and mechanism of action.

The surface marker characteristics and mechanism of action of small- to medium-sized NK suppressor lymphocytes, which can be found in both umbilical cord blood and adult peripheral blood, have been studied. Evidence suggestive of T-cell origin of the lymphocytes consisted of E-rosette formation, reactivity with OKT3 monoclonal antibody, and dot-like acid alpha-naphthyl acetate esterase (ANAE) staining pattern typical of T cells. Furthermore, no reactivity was seen with OKT6 and OKM1 monoclonal antibodies and the presence of intracytoplasmic immunoglobulin was excluded by indirect immunofluorescence microscopy, making the involvement of monocytes, B cells, and thymocytes less likely. As regards the mechanism of action, the role of prostaglandins was unlikely since indomethacin had no effect on the level of suppression. The role of soluble mediators was further examined by blocking cell secretion with monensin. In these experiments monensin treatment of the suppressor cells did not unwind suppression, suggesting that mechanisms other than secretion of suppressive factors were operative. The importance of cell-to-cell contact was demonstrated by the following observations: (i) A short contact of effector lymphocytes with suppressor lymphocytes, followed by their physical separation, resulted in decreased cytotoxic activity of the effector cells. (ii) Suppression could be mediated through Nuclepore filters, which allowed cell processes to pass through the filter, but not through filters which did not allow cell-to-cell contact. The suppressor cells were resistant to irradiation (2500 rad) and treatment with dexamethasone and puromycin. Viable cells were not needed, since paraformaldehyde-fixed suppressor cells could also mediate inhibition of K562 killing.