Quinacrine inhibits the primary but not secondary proliferative response of human cytotoxic T cells to allogeneic non-T cell antigens

Quinacrine inhibited the generation of cytotoxic T lymphocytes from human peripheral blood T cells stimulated by allogeneic non-T cells as measured by [³H]thymidine incorporation as well as by cytolytic reactions against ⁵¹Cr-labeled allogeneic lymphocytes. These observations were further supported by the finding that quinacrine inhibited the expression of Tac antigen, the receptor for growth factor(s). Because other phospholipase A₂ inhibitors such as tetracaine and p-bromophenacyl bromide could inhibit these reactions, the inhibition of cytotoxic T lymphocyte responses by quinacrine appeared to be attributable to the inhibition of phospholipase A₂ in these cells. In keeping with this interpretation, arachidonate release from phospholipids in cytotoxic T cells stimulated by allogeneic non-T cells was inhibited by quinacrine. In contrast, the pretreatment of T cells with quinacrine did not result in the inhibition of their secondary proliferactive response to the same stimulation with allogeneic non-T cells. These results, taken together, suggest that quinacrine does not inhibit the recognition of antigens by cytotoxic T cells, while it blocks the mitogenic response of T cells to allogeneic antigens.