Suppression of acquired immunity against Listeria monocytogenes by amphotericin B-mediated inhibition of CD8 of T cell function

Amphotericin B is frequently used for the treatment of fungal infections of immunocompromised individuals. Whereas immunomodulatory side effects of th is agent are known, the influence of amphotericin B was studied in the mode l of murine Listeria monocytogenes infection. Treatment of L. monocytogenes -immune mice with a nontoxic dose of amphotericin B (0.75 mg/kg) reduced an tilisterial protection by 4-5 orders of magnitude, while it had no signific ant effect on natural immunity against L. monocytogenes in naive mice. Trea tment of mice with amphotericin B also abolished the protection mediated by transfer of an L. monocytogenes-specific CD8 T cell line. Furthermore, in vitro analysis showed that amphotericin B impaired target cell lysis and in terferon-gamma production by peptide-specific CD8 T-cell lines and antigen presentation by L. monocytogenes-infected macrophagelike cells, These data indicate that amphotericin B has a strong suppressive effect on the functio n of CD8 T cells in vitro and in vivo.