Kägi D, Ledermann B, Bürki K, Hengartner H, Zinkernagel R M
Institute of Experimental Immunology, Department of Pathology, University of Zürich, Switzerland.
Eur J Immunol. 1994 Dec;24(12):3068-72. doi: 10.1002/eji.1830241223.
Growth of Listeria monocytogenes is mainly controlled by macrophages, which are activated by specific T cells. A potential role of CD8+ T cells by direct lysis of infected cells was investigated in perforin-deficient mice generated by homologous recombination. The absence of perforin-mediated cytotoxicity resulted in delayed clearance of Listeria from the spleen but not the liver after primary infection, overall susceptibility to Listeria however was not increased. Protection against a secondary infection was drastically impaired in perforin-deficient mice. Adoptive transfer of immune spleen cells to recipients revealed that anti-Listeria protection by CD8+ T cells from perforin-deficient versus normal mice was about 10-fold reduced in livers and about 100-fold reduced in the spleen of recipients. CD4+ T cells from immune control and perforin-deficient mice conferred comparable protection. These results indicate that the protective effect of CD8+ T cells against an intracellular bacterium mainly evident in secondary infection is mediated by a perforin-dependent pathway, presumably cytotoxicity, and less by other direct or indirect effector mechanisms.
单核细胞增生李斯特菌的生长主要受巨噬细胞控制，巨噬细胞由特定的T细胞激活。通过同源重组产生的穿孔素缺陷小鼠，研究了CD8 + T细胞通过直接裂解感染细胞的潜在作用。穿孔素介导的细胞毒性缺失导致初次感染后脾脏中李斯特菌的清除延迟，但肝脏中没有，然而对李斯特菌的总体易感性并未增加。穿孔素缺陷小鼠对二次感染的保护作用严重受损。将免疫脾细胞过继转移给受体显示，来自穿孔素缺陷小鼠与正常小鼠的CD8 + T细胞对受体肝脏中抗李斯特菌的保护作用降低了约10倍，在脾脏中降低了约100倍。来自免疫对照和穿孔素缺陷小鼠的CD4 + T细胞提供了相当的保护作用。这些结果表明，CD8 + T细胞对细胞内细菌的保护作用主要在二次感染中明显，是由穿孔素依赖性途径介导的，可能是细胞毒性，而较少由其他直接或间接效应机制介导。
