Selective inhibition of functional lymphocyte subpopulations by ribavirin

Abstract

The present studies were designed to examine the effects of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), a broad-spectrum antiviral agent, on the generation of murine antibody responses in vitro. Whereas primary and secondary sheep erythrocyte-specific, plaque-forming cell responses by normal murine spleen cells were enhanced by low concentrations of ribavirin (1 microgram per culture), they were strongly inhibited by higher concentrations of ribavirin (5 to 10 micrograms per culture). Both phenomena occurred with the greatest magnitude when spleen cells were exposed to ribavirin 48 to 72 h after culture initiation. Enhancement appeared to result from selective interference with suppressor T cells, since ribavirin failed to augment lipopolysaccharide-specific plaque-forming cell responses in T cell-depleted spleen cell cultures but inhibited concanavalin A-induced lymphocyte proliferation and suppressor T cell generation in cultures of normal spleen cells. The immunosuppressive properties of ribavirin were mediated by a direct antiproliferative effect and, at higher concentrations, a cytotoxic effect for B lymphocytes, since the drug inhibited plaque-forming cell responses in T cell-depleted spleen cell cultures, suppressed lipopolysaccharide-induced lymphocyte proliferation and reduced viable spleen cell recoveries.