Tetranactin, a macrotetrolide antibiotic, suppresses in vitro proliferation of human lymphocytes and generation of cytotoxicity.

Abstract

Tetranactin, a hydrophobic cyclic antibiotic produced by Streptomyces aureus, has previously been shown to suppress in vitro activation of rat lymphocytes by concanavalin A as well as the onset of experimental autoimmune uveoretinitis in Lewis rats. Here we report the effects of tetranactin on human T and NK lymphocytes in vitro. Tetranactin, at concentrations up to 100 ng/ml, was not toxic to human lymphocytes but completely abrogated the proliferation of human T lymphocytes in response to allogeneic cells in mixed lymphocyte cultures. Tetranactin also blocked the initiation of proliferation in response to interleukin-2, but did not block proliferation of interleukin-2-activated cells. Tetranactin also blocked generation of cytotoxic T lymphocytes and activated killer cells in the mixed lymphocyte culture. However, up to 100 ng/ml tetranactin did not alter the lytic activity of cytotoxic T or NK lymphocytes generated in its absence. The ability of low doses of tetranactin to block the induction of lymphoproliferation is similar to the action of cyclosporin A. Since cyclosporin A is also a cyclic hydrophobic molecule, the immunosuppressive actions of these two agents may involve a similar mechanism.