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.