Expression of CD95 ligand on parenchymal, epithelial, or tumor cells has been suggested to downregulate the immune response and to control lymphocyte activation. Suppression might be mediated by induction of apoptosis or by inhibition of Ca(2+) channels upon CD95 triggering. We, therefore, aimed to employ this model to modify the immune response to an antigen presented to cytotoxic T cells by antigen-presenting MC57 cells. This model would be very useful to specifically downregulate the immune response to autoantigens in autoimmune situations. However, cytotoxic T cell lines tested in the present study were resistant to CD95 ligand expression on antigen-presenting MC57 cells. In addition, coincubation of the lymphocytes with antigen presenting cells failed to block cytotoxicity mediated by the T lymphocytes. We, therefore, conclude that single expression of CD95 ligand on antigen-presenting cells is insufficient to specifically downregulate an immune response by CD8(+-)triggered immune response.