MOUSE LYMPHOBLASTS LOSE THEIR IMMUNOGENICITY AND SUSCEPTIBILITY TO SPECIFIC CYTOTOXIC T-LYMPHOCYTE LYSIS DURING MAINTENANCE IN CULTURE

This study was undertaken to search for possible mechanisms by which T -cell lines become nonimmunogenic and refractory to cellular-mediated lysis during culture. We demonstrate that mouse lymphoblasts (LB) lost their susceptibility to specific cytotoxic T lymphocyte (CTL)-mediate d lysis following culture for more than 5 days in the presence interle ukin-2 (IL-2), IL-7 but not IL-4. In contrast, the cultured lymphoblas ts (CLB) were efficiently lysed by specific antibody and C' and by CTL in the presence of concanavalin A. In addition, CLB did not inhibit c ytotoxicity against LB in a cold target competition assay, indicating that CLB and LB differ in the expression of certain surface molecules. Indeed, a significantly lower expression of H-2D class I antigen, the Fas antigen and the adhesion molecules intracellular adhesion molecul e-1 (ICAM-1) and very late activation antigen-4 (VLA-4) was observed o n the CLB surface. Consequently, CLB could not form conjugates with sp ecific CTL, a prerequisite for CTL-mediated lysis. In addition, there was a marked decrease in CLB immunogenicity: the cultured cells were u nable to stimulate allogeneic spleen cells in mixed lymphocyte culture nor could they induce a cytotoxic response following their injection into allogeneic mice. The reduced immunogenicity enabled the prolonged survival of active CLB in an allogeneic host. We suggest that the ext ended survival in an allogeneic tumour-bearing host of cultured, hence weakly immunogenic, anti-tumour CTL, will enable them the in vivo imp lementation of their anti-tumour activity.