Immunomodulation of murine experimental autoimmune encephalomyelitis by pertussis toxin: the protective activity, but not the disease-enhancing activity, can be attributed to the nontoxic B-oligomer.
Bordetella pertussis and its major virulence component, pertussis toxin (PT), have been used routinely to promote the development of such murine experimental autoimmune diseases as experimental autoimmune encephalomyelitis (EAE). Recently, we reported that B. pertussis also can protect against EAE. The protective activity was assigned to PT, a complex holomer composed of an A-promoter, the toxic S1 subunit, and a B-oligomer comprised of subunits S2, S3, S4, and S5. Although some data are available to explain how PT can enhance the development of EAE, nothing is known about the mechanism by which it protects against the disease. Toward understanding how PT can have such conflicting effects on EAE, we investigated the immunomodulatory activity of the various components of PT. Herein we show that the enhancing and protective activities reside within different regions of the PT holomer. Thus, though S1 appeared essential in imparting enhancing activity to PT, it played no role of importance in disease protection, and the protective effects of PT could be assigned fully to the B-oligomer. Further investigation with gel-purified PT subunits revealed that B-oligomer subunits protected against EAE to varying extent, with S3 being the most protective. These data suggest a potential therapeutic application for the B-oligomer or some of its subunits, which appear to be potent protective agents, without the toxicity or disease-promoting activity associated with PT.
Ben-Nun
A
A
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Mendel
I
I
Kerlero de Rosbo
N
N
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology / Q000472:pathogenicity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D051379:Mice; D015394:Molecular Structure; D037342:Pertussis Toxin; D014774:Virulence / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000276:Adjuvants, Immunologic; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin