Cell-mediated and glucocorticoid-mediated target cell lysis do not appear to share common pathways

Target cell lysis by cytolyic lymphocytes follows a sequence of events that culminate in osmotic destruction of the target. Although it is clear that killer cell derived components play a crucial role in target cell lysis it is not clear to what extent the target itself is involved in its destruction. Recent observations have pointed to the possibility that glucocorticoid mediated and cell mediated lysis may utilize common pathways of cell lysis. In analyzing this question we found that cell lines that have nonfunctional glucocorticoid receptors like S49-78 and S49-88 are good targets for both NK and thymus-derived killer (TK) cells. Cell lines that are glucocorticoid sensitive such as Q1(4)6 are sensitive to NK-mediated lysis as its derivative HL4-6-3 which contains glucocorticoid receptors but is glucocorticoid resistant. An intriguing exception to this is the glucocorticoid-resistant mutant S49-4RD which is relatively resistant to both NK and TK lysis compared with parent S49. The resistance of S49-4RD to cell-mediated lysis we show here is most likely due to a defect in the target which results in its failure to trigger the cytolytic machinery in the killer cell rather than in its resistance to lysis per se. In support of this we demonstrate that lysis of S49-4RD by cytolytic granules from TK cells is normal. Moreover TK cells lyse S49-4RD as efficiently as its parent in the presence of the lectin Con A. The conclusion that S49-4RD has a defect in its ability to induce killer cells to initiate the cytolytic reaction is also in agreement with the finding that TK-S49-4RD conjugates show inefficient reorientation of the Golgi apparatus in the effector.