Gene expression in antigen-specific CD8+ T cells during viral infection
Gene expression in antigen-specific CD8+ T cells during viral infection
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DOI：
10.4049/jimmunol.166.2.795
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发表时间：
2001-01-15
影响因子：
4.4
通讯作者：
Ahmed, R
中科院分区：
文献类型：
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作者：
Grayson, JM;Murali-Krishna, K;Ahmed, R
感染细胞内病原体后，抗原特异性CD8(+)T细胞被激活并开始增殖。当这些细胞被激活时，它们就会发挥效应功能，包括细胞因子的产生和细胞溶解。在感染被清除后，免疫系统通过大多数抗原特异性效应细胞的凋亡恢复到动态平衡。存活的记忆细胞可以持续更长的时间，并提供防止再次感染的保护。人们对抗原特异性细胞在发育过程中基因表达的变化知之甚少，即从幼稚到效应再到记忆。我们用重组MHC-I类四聚体从感染淋巴细胞性脉络膜脑膜炎病毒的小鼠不同时间点分离出抗原特异性CD8(+)T细胞，并进行半定量RT-PCR，我们检测了与细胞周期调控有关的基因，2)效应和调节功能，以及3)凋亡易感性，我们发现抗原特异性CD8(+)记忆T细胞表达高水平的Bcl2，Bax，干扰素-γ和肺Kruppel样因子(LKLF)，而p21和p27mRNA水平降低。此外，幼稚细胞和记忆细胞之间的基因表达模式是不同的，这表明这两种细胞类型通过不同的机制控制对凋亡的敏感性。
Following infection with intracellular pathogens, Ag-specific CD8(+) T cells become activated and begin to proliferate. As these cells become activated, they elaborate effector functions including cytokine production and cytolysis. After the infection has been cleared, the immune system returns to homeostasis through apoptosis of the majority of the Ag-specific effector cells. The surviving memory cells can persist for extended periods and provide protection against reinfection. Little is known about the changes in gene expression as Ag-specific cells progress through these stages of development, i.e., naive to effector to memory. Using recombinant MHC class I tetramers, we isolated Ag-specific CD8(+) T cells from mice infected with lymphocytic choriomeningitis virus at various time points and performed semiquantitative RT-PCR, We examined expression of: 1) genes involved in cell cycle control, 2) effector and regulatory functions, and 3) susceptibility to apoptosis, We found that Ag-specific CD8(+) memory T cells contain high steady-state levels of Bcl-2, Bax, IFN-gamma, and lung Kruppel-like factor (LKLF), and decreased levels of p21 and p27 mRNA. Moreover, the pattern of gene expression between naive and memory cells is distinct and suggests that these two cell types control susceptibility to apoptosis through different mechanisms.