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

进行本研究以分析涉及对包括李斯特菌和分枝杆菌在内的胞内细菌诱导细胞介导的免疫的共同机制，并获得以下结果。（1）杀死的细菌细胞在诱导特异性免疫中的无效性并不归因于抗原的量或细菌抗原在小鼠中的存在。(2)T在用活细菌免疫后小鼠中产生的细胞可以被活的和杀死的细菌细胞激活，HSP的存在不是诱导保护性T细胞的原因。（3）在众多的单细胞增生乳杆菌菌株中，有些菌株即使作为活菌疫苗也不能诱导特异性免疫。诱导保护性免疫的能力与每种菌株诱导巨噬细胞产生IL-1的能力相关。（4）重组IL-1沿着灭活菌免疫可显著促进小鼠体内抗原特异性T细胞的发育。（5）李斯特菌诱导IL-1的能力主要来源于产生58 kDa溶血素-β-溶血素O。（6）IFN-γ的产生对于抗原特异性CD 4 T细胞表达保护性免疫是必不可少的，而那些产生除IFN-γ以外的细胞因子的T细胞不能提供保护性免疫。产生能力对于抗原特异性CD 4 ^+ T细胞最终表达保护性免疫是必不可少的。

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.