Sasaki T, Mieno M, Udono H, Yamaguchi K, Usui T, Hara K, Shiku H, Nakayama E
Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan.
J Exp Med. 1990 Apr 1;171(4):1141-54. doi: 10.1084/jem.171.4.1141.
Studies were made on the effects of in vivo administration of anti-CD4 mAb, anti-CD8 mAb, or a combination of both mAbs on multiplication of bacteria, the levels of serum transaminases, and mortality in mice infected with Listeria monocytogenes. Results showed that in sublethal infection, CD8+ cells enhanced the peak of bacterial multiplication and liver cell necrosis, and CD4+ cells suppressed CD8+ cell-mediated enhancement. Results also showed that either CD4+ or CD8+ cells were necessary for, and capable of, mediating clearance of the bacteria. CD8+ cells were more efficient than CD4+ cells, but for optimal clearance both were necessary. In lethal listeriosis, treatment of mice with anti-CD8 mAb or a combination of both anti-CD4 and anti-CD8 mAbs, but not anti-CD4 mAb only, protected mice from death by decreasing multiplication of bacteria in the liver and spleen after a peak of approximately 10(8) CFU, and lowering the elevated serum levels of transaminases. These findings indicated that CD8+ cells were responsible for causing irreversible systemic Listeria infection and severe liver necrosis. In lethal listeriosis, administration of rMuIFN-gamma markedly prolonged survival by decreasing multiplication of bacteria and promoting recovery from liver necrosis.
研究了体内给予抗CD4单克隆抗体、抗CD8单克隆抗体或两者联合使用对感染单核细胞增生李斯特菌小鼠的细菌增殖、血清转氨酶水平及死亡率的影响。结果显示,在亚致死感染中,CD8+细胞增强了细菌增殖峰值和肝细胞坏死,而CD4+细胞抑制了CD8+细胞介导的增强作用。结果还表明,CD4+或CD8+细胞对于介导细菌清除是必要的且有能力介导。CD8+细胞比CD4+细胞更有效,但要实现最佳清除两者都必不可少。在致死性李斯特菌病中,用抗CD8单克隆抗体或抗CD4与抗CD8单克隆抗体联合治疗小鼠,而非仅用抗CD4单克隆抗体,可通过在约10(8)CFU峰值后减少肝脏和脾脏中的细菌增殖以及降低升高的血清转氨酶水平来保护小鼠免于死亡。这些发现表明CD8+细胞是导致不可逆全身性李斯特菌感染和严重肝坏死的原因。在致死性李斯特菌病中,给予重组小鼠干扰素-γ可通过减少细菌增殖和促进肝坏死恢复来显著延长生存期。