Analysis of a common mechanism for the induction of cell-mediated immunity by intracellular bacteria and its application to host defense against bacterial infection.

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This study was carried out to analyze the common mechanisms involved in the induction of cell-mediated immunity to intracellular bacteria including Listeria and Mycobacteria, and the following results were obtained. (1)The ineffectiveness of killed bacterial cells in the induction of specific immunity is not attributable to the amount of antigen or to the peristence of bacterial antigen in mice. (2)T cells generated in mice after immunization with viable bacteria could be activated by both viable and killed bacterial cells and the presence of HSP is not responsible for the induction of protective T cells. (3)Among various strains of L.monocy- togenes, some strains were found to be ineffective for the induction of specific immunity even if used as viable bacterial vaccine. The ability to induce protective immunity was correlated with the ability of each strain to induce macrophage production of IL-1. (4)Administration of recombinant IL-1 along with immunization with killed bacteria significantly promoted the development of antigen-specific T cells in mice. (5)The IL-1-inducing ability of Listeria was attributable to the production of 58KDa-hemolysin, listeriolysin O. (6)Production of IFN-gamma was indispensable for the expression of protective immunity by antigen- specific CD4 T cells and those which produce cytokine other than IFN-gamma could not afford the protective immunity.These results indicated that monokine production including IL-1 is critically required in the induction of cell-mediated immunity to intracellular bacteria and that IFN-gamma-producing ability is indispensable for the final expression of protective immunity by antigen-specific CD4^+ T cells.