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 proliferative 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.