CD8(+) T-CELL-MEDIATED PROTECTION AGAINST AN INTRACELLULAR BACTERIUM BY PERFORIN-DEPENDENT CYTOTOXICITY
CD8(+) T-CELL-MEDIATED PROTECTION AGAINST AN INTRACELLULAR BACTERIUM BY PERFORIN-DEPENDENT CYTOTOXICITY
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DOI：
10.1002/eji.1830241223
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发表时间：
1994-12-01
影响因子：
5.4
通讯作者：
ZINKERNAGEL, RM
中科院分区：
文献类型：
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作者：
KAGI, D;LEDERMANN, B;ZINKERNAGEL, RM
单核增生李斯特菌的生长主要受巨噬细胞控制，巨噬细胞被特异性T细胞激活。在同源重组产生的穿孔蛋白缺陷小鼠中，研究了CD8(+) T细胞通过直接裂解感染细胞的潜在作用。缺乏穿孔素介导的细胞毒性导致原发性感染后李斯特菌从脾脏而不是肝脏清除延迟，但对李斯特菌的总体易感性并未增加。在穿孔素缺乏的小鼠中，对继发性感染的保护能力急剧受损。将免疫脾细胞过继移植给受体后发现，与正常小鼠相比，来自穿孔素缺陷小鼠的CD8(+) T细胞在肝脏中的抗李斯特菌保护作用降低了约10倍，在受体的脾脏中降低了约100倍。来自免疫对照组和穿孔素缺陷小鼠的CD4(+) T细胞具有相当的保护作用。这些结果表明，CD8(+) T细胞对继发性感染中主要明显的细胞内细菌的保护作用是通过穿孔依赖途径介导的，可能是细胞毒性，而不是其他直接或间接的效应机制。
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.