Adjuvanticity of pertussis toxin is mediated by differential effects on the activity of T suppressor, T amplifier and T helper cells.
The immunomodulatory effects of pertussis toxin (Ptx) were studied in BALB/c mice immunized with type III pneumococcal polysaccharide (SSS-III). The antibody response to SSS-III is predominantly of the IgM class and is regulated by two opposing types of T cells, a T suppressor (TS) and a T amplifier (TA) cell. Treatment of mice with Ptx at the time of immunization with SSS-III results in an enhancement of the splenic antigen-specific IgM response, which was estimated by a plaque-forming cell assay. Numbers of non-antigen-specific IgM producing cells were not significantly affected. This adjuvant effect occurred in nu/+ but not in T cell deficient nu/nu mice. Such adjuvanticity appears to be due in part to the neutralization of TS, since (a) Ptx-treatment was found to reverse TS-mediated low-dose immunological tolerance induced in mice previously exposed to a subimmunogenic dose of SSS-III, and (b) in vitro Ptx-treatment of a cell population enriched in SSS-III-specific TS, activity abolished the capacity of such cells to transfer suppression when given to recipients at the time of immunization with SSS-III. In another type of cell transfer experiment, it was shown that Ptx treatment resulted in an increased frequency of TA in mice immunized with SSS-III. We conclude that Ptx differentially affects at least two populations of regulatory T cells, and that these effects are not directly related to the mitogenicity of Ptx for T cells or to a direct effect upon B cells.
Hasløv
K
K
Bacterial Vaccine Department, Statens Seruminstitute, Copenhagen, Denmark.
Petersen
J W
JW
Baker
P J
PJ
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D007075:Immunoglobulin M / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D037342:Pertussis Toxin; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000276:immunology*
D000276:Adjuvants, Immunologic; D007075:Immunoglobulin M; D008050:Lipid A; D011135:Polysaccharides, Bacterial; D010566:Virulence Factors, Bordetella; C026604:pneumococcal polysaccharide, type III; D037342:Pertussis Toxin; C048436:monophosphoryl lipid A