Fuse Y, Nishimura H, Maeda K, Yoshikai Y
Department of Internal Medicine, Nagoya University Branch Hospital, Nagoya University School of Medicine, Japan.
Infect Immun. 1997 May;65(5):1883-91. doi: 10.1128/iai.65.5.1883-1891.1997.
CD95 (Fas) is known to mediate activation-induced T-cell death by apoptosis. To understand the role of CD95 during the course of bacterial infection, we examined the kinetics of alphabeta and gammadelta T cells in the peritoneal cavities and livers of 5-week-old CD95-defective MRL/lpr mice after an intraperitoneal infection with Listeria monocytogenes. The number of bacteria in the spleen decreased to an undetectable level by day 10 after infection with 7 x 10(3) Listeria cells similar to the number in MRL/+/+ mice. The number of alphabeta T cells expressing CD44 and CD95 reached a maximum in the peritoneal cavity on day 6 after listerial infection and thereafter decreased gradually in MRL/+/+ mice, whereas CD44+ alphabeta T cells without CD95 expression continued to increase throughout the course of listerial infection in MRL/lpr mice. Freshly isolated T cells from MRL/+/+ mice infected with L. monocytogenes 10 days previously showed DNA fragmentation with apoptosis, whereas such fragmentation was not prominent in T cells from infected MRL/lpr mice. In correlation with the increased number of CD44+ alphabeta T cells, Listeria-specific T-cell proliferation of peritoneal exudate cells was significantly greater in MRL/lpr mice than in MRL/+/+ mice on day 10 after listerial infection. In contrast to alphabeta T cells, gammadelta T cells increased in number only transiently in the peritoneal cavity and liver after listerial infection in both MRL/lpr mice and MRL/+/+ mice. These results suggest that CD95-mediated cell death with apoptosis may be involved in termination of the alphabeta-T-cell-mediated immune response after the battle against L. monocytogenes has been won, whereas gammadelta T cells may undergo apoptosis independently of CD95 during the course of listerial infection.
已知CD95(Fas)可通过凋亡介导活化诱导的T细胞死亡。为了解CD95在细菌感染过程中的作用,我们检测了5周龄CD95缺陷型MRL/lpr小鼠腹腔和肝脏中αβ和γδ T细胞的动力学变化,这些小鼠经腹腔注射单核细胞增生李斯特菌感染。感染7×10³个李斯特菌细胞后第10天,脾脏中的细菌数量降至无法检测的水平,这与MRL/+/+小鼠中的情况相似。在李斯特菌感染后第6天,表达CD44和CD95的αβ T细胞数量在腹腔中达到最大值,此后在MRL/+/+小鼠中逐渐减少,而在MRL/lpr小鼠中不表达CD95的CD44⁺αβ T细胞在整个李斯特菌感染过程中持续增加。从10天前感染单核细胞增生李斯特菌的MRL/+/+小鼠中新鲜分离的T细胞显示出凋亡导致的DNA片段化,而在感染的MRL/lpr小鼠的T细胞中这种片段化并不明显。与CD44⁺αβ T细胞数量增加相关,在李斯特菌感染后第10天,MRL/lpr小鼠腹腔渗出细胞中李斯特菌特异性T细胞增殖明显高于MRL/+/+小鼠。与αβ T细胞不同,在MRL/lpr小鼠和MRL/+/+小鼠中,李斯特菌感染后γδ T细胞数量仅在腹腔和肝脏中短暂增加。这些结果表明,CD95介导的凋亡性细胞死亡可能参与了在战胜单核细胞增生李斯特菌后αβ T细胞介导的免疫反应的终止,而γδ T细胞在李斯特菌感染过程中可能独立于CD95发生凋亡。