Grayson J M, Murali-Krishna K, Altman J D, Ahmed R
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30332, USA.
J Immunol. 2001 Jan 15;166(2):795-9. doi: 10.4049/jimmunol.166.2.795.
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.
在受到细胞内病原体感染后，抗原特异性CD8(+) T细胞被激活并开始增殖。随着这些细胞被激活，它们发挥效应功能，包括细胞因子产生和细胞溶解。感染清除后，免疫系统通过大多数抗原特异性效应细胞的凋亡恢复到稳态。存活的记忆细胞可以长期存在并提供针对再次感染的保护。关于抗原特异性细胞在从初始状态发展到效应状态再到记忆状态的这些阶段中基因表达的变化，我们所知甚少。我们使用重组MHC I类四聚体，在不同时间点从感染淋巴细胞性脉络丛脑膜炎病毒的小鼠中分离出抗原特异性CD8(+) T细胞，并进行了半定量RT-PCR。我们检测了以下基因的表达：1）参与细胞周期调控的基因，2）效应和调节功能相关基因，3）对凋亡的易感性相关基因。我们发现，抗原特异性CD8(+)记忆T细胞中Bcl-2、BAX、IFN-γ和肺Kruppel样因子（LKLF）的稳态水平较高，而p21和p27 mRNA水平降低。此外，初始细胞和记忆细胞之间的基因表达模式不同，这表明这两种细胞类型通过不同机制控制对凋亡的易感性。
