Yang J, Mitsuyama M
Department of Bacteriology, Niigata University School of Medicine, Japan.
Immunology. 1997 Aug;91(4):529-35. doi: 10.1046/j.1365-2567.1997.00288.x.
Protective CD4+ T cells against Mycobacterium bovis bacillus Calmette-Guérin (BCG), which are characterized by the ability to produce interferon-gamma (IFN-gamma), could be induced by immunization of mice with viable BCG but not with killed BCG. A high level of IFN-gamma mRNA was observed when normal spleen cells were stimulated with viable but not killed BCG. By comparing mice immunized with either viable or killed M. bovis BCG, it was found that a high level of IFN-gamma mRNA was expressed only after immunization with viable BCG. This finding prompted us to investigate the effect of neutralizing the IFN-gamma on the final generation of protective T cells against M. bovis BCG. When endogenous IFN-gamma was neutralized by administration of anti-IFN-gamma monoclonal antibody in mice immunized with viable BCG, the generation of protective T cells was significantly impaired, as revealed by the adoptive transfer of spleen T cells. The generation of BCG-specific, IFN-gamma-producing T cells was also abolished. These results clearly demonstrate that endogenous IFN-gamma actually plays a critical role in the generation of protective T cells against M. bovis BCG in vivo. Moreover, this study suggests that the lack of IFN-gamma-inducing ability is responsible for the inability of killed M. bovis BCG to induce protective T cells in mice.
针对卡介苗（BCG）的保护性CD4 + T细胞，其特征在于能够产生γ干扰素（IFN-γ），可通过用活卡介苗免疫小鼠诱导产生，而用灭活卡介苗则不能。当用活卡介苗而非灭活卡介苗刺激正常脾细胞时，观察到高水平的IFN-γ mRNA。通过比较用活卡介苗或灭活卡介苗免疫的小鼠，发现仅在用活卡介苗免疫后才表达高水平的IFN-γ mRNA。这一发现促使我们研究中和IFN-γ对针对卡介苗的保护性T细胞最终生成的影响。在用活卡介苗免疫的小鼠中，通过给予抗IFN-γ单克隆抗体中和内源性IFN-γ时，如脾T细胞的过继转移所示，保护性T细胞的生成明显受损。卡介苗特异性、产生IFN-γ的T细胞的生成也被消除。这些结果清楚地表明，内源性IFN-γ实际上在体内针对卡介苗的保护性T细胞的生成中起关键作用。此外，本研究表明，缺乏IFN-γ诱导能力是灭活卡介苗不能在小鼠中诱导保护性T细胞的原因。
