Immune suppression and induction of gamma interferon by pertussis toxin.
It has been suggested that pertussis toxin is a virulence factor of Bordetella pertussis. Although extracts enriched in pertussis toxin activity have been reported to enhance immune responsiveness, other studies have demonstrated a suppressive ability, suggesting that the toxin may contribute to the virulence of B. pertussis through mechanisms involving immune suppression. We report that purified pertussis toxin suppressed the in vitro immunoglobulin M antibody response of mouse splenocytes to sheep erythrocytes. At submitogenic doses, the toxin also suppressed [3H]thymidine incorporation by splenocytes, suggesting that it interfered with antibody formation by inhibiting lymphocyte proliferation. Antiviral activity was detected in culture supernatants obtained from pertussis toxin-suppressed splenocyte cultures by using a cytopathic effect inhibition assay. This antiviral activity was virus nonspecific, sensitive to pH 2.0 treatment, stable to heating at 56 degrees C, and neutralized by anti-gamma interferon antiserum. Finally, the fractionation of splenocytes by anti-immunoglobulin panning techniques suggested that Lyt2+ lymphocytes proliferated in response to pertussis toxin and produced interferon. Our results suggest that pertussis toxin may contribute to the virulence of B. pertussis through stimulation of Lyt2+ lymphocytes, resulting in the induction of gamma interferon and the subsequent inhibition of the primary antibody response.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000950:Antigens, Ly / Q000276:immunology; D001427:Bacterial Toxins / Q000494:pharmacology*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D037342:Pertussis Toxin; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D010566:Virulence Factors, Bordetella; D014779:Virus Replication / Q000187:drug effects
D000950:Antigens, Ly; D001427:Bacterial Toxins; D010566:Virulence Factors, Bordetella; D007371:Interferon-gamma; D037342:Pertussis Toxin