Suppression of acquired immunity against Listeria monocytogenes by amphotericin B-mediated inhibition of CD8 T cell function.
Amphotericin B is frequently used for the treatment of fungal infections of immunocompromised individuals. Whereas immunomodulatory side effects of this agent are known, the influence of amphotericin B was studied in the model of murine Listeria monocytogenes infection. Treatment of L. monocytogenes-immune mice with a nontoxic dose of amphotericin B (0.75 mg/kg) reduced antilisterial protection by 4-5 orders of magnitude, while it had no significant effect on natural immunity against L. monocytogenes in naive mice. Treatment 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 interferon-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 function of CD8 T cells in vitro and in vivo.
Geginat
G
G
Institut für Medizinische Mikrobiologie und Hygiene, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, 68167 Mannheim, Germany.
Kretschmar
M
M
Walter
S
S
Junker
D
D
Hof
H
H
Nichterlein
T
T
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000666:Amphotericin B