T-CELL-MEDIATED CYTOTOXICITY OF HUMAN GLIOMAS - A TUMOR NECROSIS FACTOR-INDEPENDENT MECHANISM

CELLULAR IMMUNE EFFECTOR mechanisms are implicated as potential therap ies for malignant gliomas. We have examined the potential for anti-CD3 -activated human peripheral blood-derived CD4(+) and CD8(+) T cells to induce lysis of human glioma cell lines in vitro, the mechanism of ac tion of these cells, and the capacity of the glioma to inhibit the eff ect. We found that activated CD4(+) and CD8(+) T cell preparations con taining less than 5% natural killer cells could induce significant lys is of the glioma cell line U251, as measured by an is-hour, but not 5- hour, chromium-51 or lactate dehydrogenase release assay. This effect was not reproduced using recombinant tumor necrosis factor or inhibite d with antitumor necrosis factor antibody. Anti-lymphocyte functional antigen-1 and anti-intercellular adhesion molecule antibodies also did not inhibit the effect. Glioma-derived supernatant could inhibit the proliferation of the T cells but not the cytotoxic effect. Human fetal astrocytes were also susceptible to the cytotoxic effect of the activ ated T cells. These results indicate that activated T cells can induce glioma cytotoxicity via a mechanism independent of tumor necrosis fac tor. The therapeutic potential of this effector mechanism will depend on its capacity to deliver these cells or their specific effector mole cules to the tumor site or to augment the activity of such cells, whic h accumulate naturally in gliomas.