Abrogation of suppression of delayed hypersensitivity induced by Candida albicans-derived mannan by treatment with monophosphoryl lipid A

Abstract

Monophosphoryl lipid A (MLA), derived either from Salmonella minnesota or Salmonella typhimurium, was tested for its ability to alter Candida albicans mannan (MAN)-specific suppression. Since we showed previously that naive mice injected intravenously (i.v.) with MAN developed suppressor T cells capable of down-regulating delayed-type hypersensitivity when transferred to immunized recipients, MLA was tested for its ability to influence suppressor activity in the donors of suppressor cells. T-lymphocyte-enriched suspensions from donor mice treated with MLA, especially that derived from S. typhimurium, 2 or 3 days after the injection of MAN lost the ability to suppress delayed-type hypersensitivity when transferred to immunized mice. Transferable suppressor activity was reduced but not always completely abrogated when donor animals were treated with MLA 1 day following the administration of MAN. In several experiments, S. minnesota MLA also abrogated activity, but it was not effective in other transfer experiments. In a different type of experiment, MLA was given to immunized mice which had been suppressed directly with MAN. Mice were immunized, either by the introduction of C. albicans intragastrically followed by inoculation intradermally (i.d.) or by two i.d. inoculations, and MAN-specific suppressor cells were induced in such animals by the i.v. injection of MAN 1 day before the first or second i.d. inoculation in animals given intragastric plus i.d. inoculations and those given two i.d. inoculations, respectively. MLA was administered to such mice prior to the i.v. injection of MAN, on the same day, or 1 to 4 days thereafter. S. typhimurium MLA, especially when given to mice 2 days following the administration of MAN, caused a partial abrogation of suppressor activity. Overall, however, MLA, at 5 to 100 micrograms, had variable and minimal effects on suppressor activity in immunized mice suppressed by the i.v. administration of MAN. In summary, MLA is clearly capable of abrogating MAN-induced suppression when given to nonimmunized animals in which MAN-specific suppressor cells had been induced, but its efficacy in immunized animals suppressed by the i.v. administration of MAN was marginal.