ABROGATION OF SUPPRESSION OF DELAYED-HYPERSENSITIVITY INDUCED BY CANDIDA-ALBICANS-DERIVED MANNAN BY TREATMENT WITH MONOPHOSPHORYL LIPID-A

Monophosphoryl lipid A (MLA), derived either from Salmonella minnesota or Salmonella typhimurium, was tested for its ability to alter Candid a albicans mannan (MAN)-specific suppression. Since we showed previous ly that naive mice injected intravenously (i.v.) with MAN developed su ppressor T cells capable of down-regulating delayed-type hypersensitiv ity when transferred to immunized recipients, MLA was tested for its a bility to influence suppressor activity in the donors of suppressor ce lls. T-lymphocyte-enriched suspensions from donor mice treated with MI A, especially that derived from S. typhimurium, 2 or 3 days after the injection of MAN lost the ability to suppress delayed-type hypersensit ivity when transferred to immunized mice. Transferable suppressor acti vity was reduced but not always completely abrogated when donor animal s 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 o f experiment, MLA was given to immunized mice which had been suppresse d directly with MAN. Mice were immunized, either by the introduction o f C albicans intragastrically followed by inoculation intradermally (i .d.) or by two i.d. inoculations, and MAN-specific suppressor cells we re induced in such animals by the i.v. injection of MAN 1 day before t he first or second i.d. inoculation in animals given intragastric plus i.d. inoculations and those given two i.d. inoculations, respectively . MIA 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, espe cially 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 mug, had variable and minimal effects on suppressor a ctivity in immunized mice suppressed by the i.v. administration of MAN . In summary, MIA is clearly capable of abrogating MAN-induced suppres sion when given to nonimmunized animals in which MAN-specific suppress or cells had been induced, but its efficacy in immunized animals suppr essed by the i.v. administration of MAN was marginal.